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1. Author Correction: Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L, Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A, Baecklund, Eva, Brun, Johan G, Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B, Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V, Kvarnström, Marika, Kelly, Jennifer A, Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M, Taylor, Kimberly E, Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J, Grundahl, Kiely M, Hefner, Kimberly S, Radfar, Lida, Lewis, David M, Stone, Donald U, Kaufman, C Erick, Brennan, Michael T, Guthridge, Joel M, James, Judith A, Scofield, R Hal, Gaffney, Patrick M, Criswell, Lindsey A, Jonsson, Roland, Eriksson, Per, Bowman, Simon J, Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E, PRECISESADS Clinical Consortium, Shiboski, Caroline H, Sjögren’s International Collaborative Clinical Alliance (SICCA), Wahren-Herlenius, Marie, Ng, Wan-Fai, UK Primary Sjögren’s Syndrome Registry, Sivils, Kathy L, Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J
Subjects: Multidisciplinary, General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Published: 2022

2. Variability of Primary Sjögren's Syndrome Is Driven by Interferon α and Interferon α Blood Levels Are Associated With the Class II HLA–DQ Locus

Author: Trutschel, Diana, Bost, Pierre, Mariette, Xavier, Bondet, Vincent, Llibre, Alba, Posseme, Celine, Charbit, Bruno, Thorball, Christian W., Jonsson, Roland, Lessard, Christopher J., Felten, Renaud, Ng, Wan Fai, Chatenoud, Lucienne, Dumortier, Hélène, Sibilia, Jean, Fellay, Jacques, Brokstad, Karl A., Appel, Silke, Tarn, Jessica R., Quintana‐Murci, Lluis, Mingueneau, Michael, Meyer, Nicolas, Duffy, Darragh, Schwikowski, Benno, Gottenberg, Jacques Eric, Dernis, Emmanuelle, Devauchelle‐Pensec, Valerie, Dieude, Philippe, Dubost, Jean‐Jacques, Fauchais, Anne‐Laure, Goeb, Vincent, Hachulla, Eric, Hatron, Pierre Yves, Larroche, Claire, Le Guern, Véronique, Morel, Jacques, Perdriger, Aleth, Salliot, Carinne, Rist, Stephanie, Saraux, Alain, Vittecoq, Olivier, Nocturne, Gaétane, Ravaud, Philippe, Seror, Raphaèle, Abel, Laurent, Alcover, Andres, Aschard, Hugues, Astrom, Kalla, Bousso, Philippe, Bruhns, Pierre, Cumano, Ana, Demangel, Caroline, Deriano, Ludovic, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gelpi, Odile, GompertsBoneca, Ivo, Hasan, Milena, Hercberg, Serge, Lantz, Olivier, Leclerc, Claude, Mouquet, Hugo, Pellegrini, Sandra, Pol, Stanislas, Rausell, Antonio, Rogge, Lars, Sakuntabhai, Anavaj, Schwartz, Olivier, Shorte, Spencer, Soumelis, Vassili, Tangy, Frédéric, Tartour, Eric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie‐Noëlle, Albert, Matthew L., Biomédecine computationelle des systèmes / Computational systems biomedicine, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie Translationnelle - Translational Immunology lab, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), Lausanne University Hospital, University of Bergen (UiB), Oklahoma Medical Research Foundation (OMRF), University of Oklahoma Health Sciences Center (OUHSC), Université de Strasbourg (UNISTRA), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biogen Inc. [Cambridge, MA, USA], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Supported by the Innovative Medicines Initiative 2 Joint Undertaking (JU) (grant 806975). The JU receives support from the European Union’s Horizon 2020 research and innovation program and the European Unionand the European Federation of Pharmaceutical Industries and Associations. This work was also supported by the National Institutes of Health (National Institute of Arthritis and Musculoskeletal Skin Disease grant R01-AR-065953). The Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome(ASSESS) national multicenter prospective cohort was formed in 2006 with aFrench Ministry of Health grant (Programme Hospitalier de Recherche Clinique 2005 P060228). The ASSESS cohort is promoted by the French Society of Rheumatology and receives research grants from the French Society of Rheumatology. Dr. Gottenberg’s work was supported by Bristol Myers Squibbfor transcriptomic analysis of the ASSESS and Norwegian cohorts and by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögrenet des syndromes secs). Drs. Trutschel’s and Schwikowski’s work was supported by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögren et des syndromes secs)., Milieu Intérieur Consortium, ASSESS study investigators, and NECESSITY Consortium: Emmanuelle Dernis, Valerie Devauchelle-Pensec, Philippe Dieude, Jean-Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Pierre Yves Hatron, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Carinne Salliot, Stephanie Rist, Alain Saraux, Jean Sibilia, Olivier Vittecoq, Gaétane Nocturne, Philippe Ravaud, Raphaèle Seror, Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Odile Gelpi, Ivo GompertsBoneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Eric Tartour, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L Albert, Darragh Duffy, Lluis Quintana-Murci., European Project: 806975,NECESSITY, Clauss, Isabelle, and NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients - NECESSITY - 0000-00-00 - 0000-00-00 - 806975 - VALID
Subjects: Proteomics, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sjogren's Syndrome, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, HLA-DQ Antigens, Immunology, Humans, Interferon-alpha, Immunology and Allergy, Prospective Studies
Abstract: Objective: Primary Sjögren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS. Methods: We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-α (IFNα) and IFNγ protein concentrations using digital single molecular arrays (Simoa). Results: Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFNα and not by IFNγ protein levels. IFNα protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFNα protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA–DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells. Conclusion: We identified the predominance of IFNα as a driver of primary SS variability, with IFNα demonstrating an association with HLA gene polymorphisms., Arthritis & Rheumatology, 74 (12), ISSN:2326-5191, ISSN:2326-5205
Published: 2022

3. Variability in primary Sjögren's syndrome is driven by interferon alpha, and genetically associated with the class II HLA DQ locus

Author: Trutschel, Diana, Bost, Pierre, Mariette, Xavier, Bondet, Vincent, Llibre, Alba, Posseme, Céline, Charbit, Bruno, Thorball, Christian, Jonsson, Roland, Lessard, Christopher, Felten, Renaud, Ng, Wan Fai, Chatenoud, Lucienne, Dumortier, Hélène, Sibilia, Jean, Fellay, Jacques, Brokstad, Karl, Appel, Silke, Tarn Dr, Jessica, Quintana-Murci, Lluis, Mingueneau, Michael, Meyer, Nicolas, Duffy, Darragh, Schwikowski, Benno, Gottenberg, Jacques-Eric, Intérieur Consortium, Milieu, Biomédecine computationelle des systèmes / Computational systems biomedicine, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Universität Zürich [Zürich] = University of Zurich (UZH), Hôpital Bicêtre, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie Translationnelle - Translational Immunology lab, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Institut Pasteur [Paris] (IP), Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Swedish Defence Research Agency [Stockholm] (FOI), Broegelmann Research Laboratory, Department of Clinical Science, University of Oklahoma Health Sciences Center (OUHSC), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Newcastle upon Tyne Hospitals [Newcastle, UK], NIHR Biomedical Research Centre, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, University of Bergen (UiB), Newcastle University [Newcastle], Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biogen [Cambridge, USA], Université de Strasbourg (UNISTRA), Hôpital de Hautepierre [Strasbourg], and Milieu Interieur, ASSESS investigators and NECESSITY consortium
Subjects: [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; Objective: Primary Sjögren's syndrome (pSS) is the second most frequent systemic autoimmune disease affecting 0.1% of the general population. To characterize the molecular and clinical variability across pSS patients, we integrated transcriptomic, proteomic, cellular and genetic data with clinical phenotypes in a cohort of 351 pSS patients.Methods: Blood transcriptomes and genotypes of 351 pSS patients from a multi-center prospective clinical cohort were analyzed. Replication of the transcriptomic results was performed using 3 independent cohorts (n=462 patients). Circulating IFN-alpha (IFNɑ) and IFN-gamma (IFNγ) protein concentrations were determined using digital ELISA.Results: Transcriptomic analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients. This finding was replicated in three independent cohorts. As gene expression analysis did not discriminate between type I and II interferons, we applied digital ELISA to demonstrate that the IFN transcriptomic signature was driven by circulating IFNɑ, and not IFNγ, protein levels. IFNɑ protein levels, detectable in 75% of patients, were significantly associated with clinical and immunological features of disease activity at enrollment, and with increased frequency of systemic complications during the 5-year follow-up. Genetic analysis revealed a significant association between IFNɑ protein levels, a MHC-II haplotype and anti-SSA antibody. Additional cellular analysis revealed that a MHC-II HLA-DQ locus acts through upregulation of HLA II molecules on conventional DCs.Conclusions: The present analysis identified the predominance of IFNα as driver of pSS variability and revealed an association with HLA gene polymorphisms.
Published: 2022

4. Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L, Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A, Baecklund, Eva, Brun, Johan G, Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B, Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V, Kvarnström, Marika, Kelly, Jennifer A, Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M, Taylor, Kimberly E, Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J, Grundahl, Kiely M, Hefner, Kimberly S, Radfar, Lida, Lewis, David M, Stone, Donald U, Kaufman, C Erick, Brennan, Michael T, Guthridge, Joel M, James, Judith A, Scofield, R Hal, Gaffney, Patrick M, Criswell, Lindsey A, Jonsson, Roland, Eriksson, Per, Bowman, Simon J, Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E, PRECISESADS Clinical Consortium, Shiboski, Caroline H, Sjögren’s International Collaborative Clinical Alliance (SICCA), Wahren-Herlenius, Marie, Ng, Wan-Fai, UK Primary Sjögren’s Syndrome Registry, Sivils, Kathy L, Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J
Subjects: Sjögren’s disease, Sjögren’s syndrome, sjogren´s, genome, genetic risk, Sjogren's Syndrome, Multidisciplinary, Humans, General Physics and Astronomy, Genetic Predisposition to Disease, General Chemistry, Polymorphism, Single Nucleotide, Medical Genetics, General Biochemistry, Genetics and Molecular Biology, Genome-Wide Association Study, Medicinsk genetik
Abstract: Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function. Funding Agencies|National Institutes of Health (NIH) [HHSN268200782096C, HHSN268201100011I, HHSN268201200008I, R01AR073855, R01AR065953, R01AR074310, P50AR060804, R01AR050782, R01DE018209, R33AR076803, R21AR079089]; NIDCR Sjogrens Syndrome Clinic; NIDCR Division of Intramural Research at the National Institutes of Health funds [Z01-DE000704]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy [EXC 2155, 390874280]; Research Council of Norway (Oslo, Norway) [240421, 316120]; Western Norway Regional Health Authority (Helse Vest) [911807, 912043]; Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish Society of Medicine; Swedish Cancer Society; Sjogrens Syndrome Foundation; Phileona Foundation; Stockholm County Council; Swedish Research Council [2017-000641]; Assistance Publique-Hopitaux de Paris (Ministry of Health) [P060228]; French society of Rheumatology; National Institute of Aging [RC2 AG036495, RC4 AG039029]; National Institute of Dental and Craniofacial Research (NIDCR); National Eye Institute; Office of Research on Womens Health [N01-DE-32636]; NIDCR through CIDRs NIH contract; FOREUM Foundation for Research in Rheumatology
Published: 2022

5. Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

Author: Vasileios C. Pezoulas, Andreas Goules, Fanis Kalatzis, Luke Chatzis, Konstantina D. Kourou, Aliki Venetsanopoulou, Themis P. Exarchos, Saviana Gandolfo, Konstantinos Votis, Evi Zampeli, Jan Burmeister, Thorsten May, Manuel Marcelino Pérez, Iryna Lishchuk, Thymios Chondrogiannis, Vassiliki Andronikou, Theodora Varvarigou, Nenad Filipovic, Manolis Tsiknakis, Chiara Baldini, Michele Bombardieri, Hendrika Bootsma, Simon J. Bowman, Muhammad Shahnawaz Soyfoo, Dorian Parisis, Christine Delporte, Valérie Devauchelle-Pensec, Jacques-Olivier Pers, Thomas Dörner, Elena Bartoloni, Roberto Gerli, Roberto Giacomelli, Roland Jonsson, Wan-Fai Ng, Roberta Priori, Manuel Ramos-Casals, Kathy Sivils, Fotini Skopouli, Witte Torsten, Joel A. G. van Roon, Mariette Xavier, Salvatore De Vita, Athanasios G. Tzioufas, Dimitrios I. Fotiadis, Publica, and Translational Immunology Groningen (TRIGR)
Subjects: Primary Sjogren's syndrome, Lead Topic: Individual Health, Biochemistry & Molecular Biology, Dewey Decimal Classification::500 | Naturwissenschaften::570 | Biowissenschaften, Biologie, Biophysics, Primary Sjögren’s syndrome, Biochemistry, Research Line: Machine learning (ML), Structural Biology, ddc:570, Genetics, LYMPHOMA, Lymphoma classification, ComputingMethodologies_COMPUTERGRAPHICS, Science & Technology, Data curation, Biomarkers, Data harmonization, Data sharing, Federated AI, Primary Sjögren's syndrome, Computer Science Applications, Biotechnology & Applied Microbiology, Life Sciences & Biomedicine, METHODOLOGY, TP248.13-248.65, Research Article, Biotechnology
Abstract: Graphical abstract, Highlights • Data sharing can address open issues and clinical unmet needs in rare diseases. • Data curation enhanced the cohort data quality in primary Sjögrens Syndrome (pSS). • Semantic analysis yielded 7,156 harmonized patients across 21 cohorts in pSS. • Federated tree ensembles yield explainable AI models for lymphoma development. • Salivary gland swelling & cryoglobulinemia increase the risk for lymphomagenesis., For many decades, the clinical unmet needs of primary Sjögren’s Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs.
Published: 2022

6. Author Correction: Genome-wide association study identifies Sjogrens risk loci with functional implications in immune and glandular cells (vol 13, 4287, 2022)

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Published: 2022

7. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan Gorgas, Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglæn, Jonsson, Malin Viktoria, Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Herlenius, Marie Elisabeth Wahren, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.
Published: 2022

8. Differential levels of IFNα subtypes in autoimmunity and viral infection

Author: Bondet, Vincent, Rodero, Mathieu, Posseme, Céline, Bost, Pierre, Decalf, Jérémie, Haljasmägi, Liis, Bekaddour, Nassima, Rice, Gillian, Upasani, Vinit, Herbeuval, Jean-Philippe, Reynolds, John, Briggs, Tracy, Bruce, Ian, Mauri, Claudia, Isenberg, David, Menon, Madhvi, Hunt, David, Schwikowski, Benno, Mariette, Xavier, Pol, Stanislas, Rozenberg, Flore, Cantaert, Tineke, Eric Gottenberg, J., Kisand, Kai, Duffy, Darragh, Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Biologie systémique - Systems Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Ecole Doctorale Complexité du Vivant (ED515), Sorbonne Université (SU), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tartu, University of Manchester [Manchester], Manchester University NHS Foundation Trust (MFT), Immunologie [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of Birmingham [Birmingham], Sandwell and West Birmingham NHS Trust (Sandwell General Hospital), University College of London [London] (UCL), University of Edinburgh, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Strasbourg (UNISTRA), We acknowledge support from the ANR (CE17001002) awarded to DD., ANR-16-CE17-0010,IFNX,Investigation des interferonopathies type I humaine(2016), Institut Pasteur [Paris], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, TLR activation, Adolescent, Anti-IFNα autoantibodies, Infant, Interferon-alpha, Autoimmunity, Middle Aged, IFNα subtypes, Antiviral Agents, Young Adult, IFN function, Virus Diseases, Viral infection, Child, Preschool, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Child, Aged
Abstract: International audience; Type I interferons are essential for host response to viral infections, while dysregulation of their response can result in autoinflammation or autoimmunity. Among IFNα (alpha) responses, 13 subtypes exist that signal through the same receptor, but have been reported to have different effector functions. However, the lack of available tools for discriminating these closely related subtypes, in particular at the protein level, has restricted the study of their differential roles in disease. We developed a digital ELISA with specificity and high sensitivity for the IFNα2 subtype. Application of this assay, in parallel with our previously described pan-IFNα assay, allowed us to study different IFNα protein responses following cellular stimulation and in diverse patient cohorts. We observed different ratios of IFNα protein responses between viral infection and autoimmune patients. This analysis also revealed a small percentage of autoimmune patients with high IFNα2 protein measurements but low pan-IFNα measurements. Correlation with an ISG score and functional activity showed that in this small sub group of patients, IFNα2 protein measurements did not reflect its biological activity. This unusual phenotype was partly explained by the presence of anti-IFNα auto-antibodies in a subset of autoimmune patients. This study reports ultrasensitive assays for the study of IFNα proteins in patient samples and highlights the insights that can be obtained from the use of multiple phenotypic readouts in translational and clinical studies.
Published: 2021

9. TRIM33 gene somatic mutations identified by next generation sequencing in neoplasms of patients with anti-TIF1γ positive cancer-associated dermatomyositis

Author: Cordel, Nadège, Derambure, Céline, Coutant, Sophie, Mariette, Xavier, Jullien, Denis, Debarbieux, Sébastien, Chosidow, Olivier, Meyer, Alain, Bessis, Didier, Joly, Pascal, Mathian, Alexis, Levesque, Hervé, Sabourin, Jean-Christophe, Tournier, Isabelle, Boyer, Olivier, Amoura, Zahir, Aouizerate, Jessie, Benveniste, Olivier, Brocheriou, Isabelle, Dechelotte, Benoît, Graveleau, Julie, Guerzider, Pascale, Isaac, Sylvie, Kanitakis, Jean, Lannes, Béatrice, Lazure, Thierry, Rigau, Valérie, Sibilia, Jean, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Henri Mondor, Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], CHU Rouen, Normandie Université (NU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut E3M [CHU Pitié-Salpêtrière], Service de Médecine Interne [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut des Neurosciences de Montpellier (INM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Myositis and muscle disease, Male, Somatic cell, DNA Mutational Analysis, Disease, Gene mutation, MESH: Dermatomyositis, 0302 clinical medicine, Neoplasms, Medicine, Pharmacology (medical), MESH: Neoplasms, MESH: DNA Mutational Analysis, MESH: High-Throughput Nucleotide Sequencing, Skin, MESH: Aged, MESH: DNA, High-Throughput Nucleotide Sequencing, Zinc Fingers, MESH: Transcription Factors, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Muscle, Female, MESH: Mutation, DNA sequencing, Dermatomyositis, 03 medical and health sciences, Rheumatology, Genetics, MESH: Zinc Fingers, Humans, Gene, Aged, 030203 arthritis & rheumatology, MESH: Humans, Neoplasia, business.industry, Cancer, DNA, medicine.disease, TRIM33, MESH: Male, 030104 developmental biology, Mutation, Cancer research, business, MESH: Female, Transcription Factors
Abstract: Objective To deep sequence the TRIM33 gene in tumours from patients with cancer-associated anti-TIF1γ autoantibody-positive dermatomyositis (DM) as TRIM33 somatic mutations in tumours may trigger this auto-immune disease. Methods Next generation sequencing of tumour DNA samples from patients with cancer-associated anti-TIF1γ autoantibody-positive DM. Fourteen tumours from 13 anti-TIF1γ autoantibody-positive DM individuals were sequenced along with two control tumours from non-DM individuals. Results Fourteen probable somatic variants from four tumours were identified in the TRIM33 gene. Conclusion These results are in accordance with the previous report of Pinal-Fernandez et al. and support the hypothesis of a role of TRIM33 gene mutations in the pathophysiology of anti-TIF1γ autoantibody-positive DM.
Published: 2021

10. Low CD39 Expression on B Cells Predicts the Occurrence of Anti-Drug Antibodies in RA Patients Treated with Rituximab

Author: Bitoun, Samuel, Ly, Bineta, Hässler, Signe, Paoletti, Audrey, Gleizes, Aude, Hacein-Bey, Salima, Bröet, Philippe, Pallardy, Marc, Mariette, Xavier, and Hässler, Signe
Subjects: immunology, rheumatoid arthritis, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, B-Lymphocyte, B-Lymphocyte Biologicals immunology rheumatoid arthritis, Biologicals
Published: 2021

11. Monoclonal gammopathy of clinical significance: in vivo demonstration of the anti-thrombotic effect of an acquired anti-thrombin antibody

Author: Schell, Berenice, Desconclois, Celine, Mariette, Xavier, Goujard, Cecile, Lenting, Peter J., Denis, Cecile V., and Proulle, Valerie
Subjects: Case Reports
Published: 2021

12. Additional file 1 of Response to COVID-19 mRNA vaccination in multiple myeloma is conserved but impaired compared to controls

Author: Bitoun, Samuel, Henry, Julien, Vauloup-Fellous, Christelle, Dib, Nicolas, Belkhir, Rakiba, Mouna, Lina, Joly, Candie, Desjardins, Delphine, Bitu, Marie, Le Grand, Roger, Seror, Raphaèle, Roque Afonso, Anne-Marie, and Mariette, Xavier
Abstract: Additional file 1. Supplementary figure 1. Correlation between anti-Spike IgG (Elecsys Anti-SARS-CoV-2 S, Cobas, Roche Diagnostics; cut off: 0.4 IU/ml) and neutralizing activity of anti-SARS-CoV-2 antibodies (iFlash-2019-nCoV Nab assay, Ylho; cut-off: 24 IU/ml) of Multiple myeloma and control patients. The threshold of 50 IU/mL with the anti-Spike IgG assay represents the limit established on a separate cohort, above which 98% of sample tested have detectable neutralizing activity of anti- SARS-CoV-2 antibodies as defined by the threshold of 24 IU/ml with the neutralization assay. r = 0.69 p ≤ 0,0001 Spearman test.
Published: 2021
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13. Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

Author: Hermine, Olivier, Mariette, Xavier, Tharaux, Pierre-Louis, Resche-Rigon, Matthieu, Porcher, Raphaël, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Dalibey, Sarah, Raked, Nabil, Mameri, Lakhdar, Alary, Stéphanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Montlahuc, Claire, Biard, Lucie, Charreteur, Robin, Dupré, Celine, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madeleine, Claire, DOrtenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Pavy, Stéphan, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stéphane, Baudry, Elodie, Verny, Christiane, Lefèvre, Edouard, Zaidan, Mohamad, Le Tiec, Clotilde Le Tiec, Verstuyft, Céline Verstuyft, Roques, Anne-Marie, Grimaldi, Lamiae, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Solène, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Georgin-Lavialle, Sophie, Senet, Patricia, Soria, Angèle, Parrot, Antoine, François, Hélène, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadège, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefèvre, Guillaume, Fallet, Vincent, Gottenberg, Jacques-Eric, Hansmann, Yves, Andres, Emmanuel, Bayer, Sophie, Becker, Guillaume, Blanc, Frédéric, Brin, Stéphane, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Demonsant, Eric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurélien, Heger, Bob, Hutt, Anne, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Martin, Tristan, Mertes, Paul Michel, Metzger, Catherine, Meyer, Nicolas, Nisand, Gabriel, Noll, Eric, Oberlin, Mathieu, Ohlmann-Caillard, Sophie, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Sublon, Cédric, Tayebi, Hakim, Weill, François, Mekinian, Arsène, Chopin, Dorothée, Fain, Olivier, Garnier, Marc, Krause Le Garrec, Jessica, Morgand, Marjolaine, Pacanowski, Jerome, Urbina, Tomas, Mcavoy, Chloe, Pereira, Maria, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Daguenel Nguyen, Anne, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean- Se´bastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Penet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Jesuthasan, Denis, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Vale´rie, Tre´Han, Anne, Vigna, Ve´ronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charle`ne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, Xavier, Ghosn, Jade, Bachelard, Antoine, Bironne, Timothee, Borie, Raphael, Bounhiol, Agathe, Boussard, Catherine, Chauffier, Jeanne, Chalal, Solaya, Chalal, Lynda, Chansombat, Malikhone, Crespin, Paul, Crestani, Bruno, Daconceicao, Olivia, Deconinck, Laurene, Dieude, hilippe, Dossier, Antoine, Dubert, Marie, Ducrocq, Greggory, Fuentes, Axelle, Gervais, Anne, Gilbert, Marie, Isernia, Valentina, Ismael, Sophie, Joly, Veronique, Julia, Zelie, Lariven, Sylvie, Le Gac, Sylvie, Le Pluart, Diane, Louni, Francoise, Ndiaye, Awa, Papo, Thomas, Parisey, Marion, Phung, Bao, Pourbaix, Annabelle, Rachline, Anne, Rioux, Christophe, Sautereau, Aurelie, Steg, Gabriel, Tharini, Hassan, Valayer, Simon, Vallois, Dorothee, Vermes, Paul, Volpe, Thomas, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anaïs, Zarrouk, Virginie, De Lastours, Victoire, Uzzan, Matthieu, Gamany, Naura, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, De Castro, Nathalie, Clément, Melissa, Darmont, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lengliné, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asmaa, Mariotte, Eric, Martin De Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault De Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Celli Lebras, Karine, Chabert, Julien, Djaghout, Lalia, Fauvaux, Catherine, Jegu, Anne Lise, Kozaliewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madeleine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, Sene, Damien, Burlacu, Ruxandra, Chousterman, Benjamin, Megarbane, Bruno, Richette, Pascal, Riveline, Jean-Pierre, Frazier, Aline, Vicaut, Eric, Berton, Laure, Hadjam, Tassadit, Vasquez-Ibarra, Miguel Alejandro, Jourdaine, Clément, Jacob, Aude, Smati, Julie, Renaud, Stéphane, Manivet, Philippe, Pernin, Claire, Suarez, Lydia, Semerano, Luca, Abad, Sebastien, Benainous, Ruben, Bloch Queyrat, Coralie, Bonnet, Nicolas, Brahmi, Sabrina, Cailhol, johann, Cohen, Yves, Comparon, Celine, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Giroux-Leprieur, Benedicte, Goupil De Bouille, Jeanne, Jacolot, Anne, Nunes, Hilario, Oziel, Johanna, Rathouin, Vanessa, Rigal, Marthe, Roulot, Dominique, Tantet, Claire, Uzunhan, Yurdagul, Costedoat-Chalumeau, Nathalie, Ait Hamou, Zakaria, Benghanem, Sarah, Blanche, Philippe, Canoui, Etienne, Carlier, Nicolas, Chaigne, Benjamin, Contejean, Adrien, Dunogue, Bertrand, Dupland, Pierre, Durel - Maurisse, Aurélie, Gauzit, Remy, Jaubert, Paul, Joumaa, Hassan, Jozwiak, Mathieu, Kerneis, Solen, Lachatre, Marie, Lafoeste, Hélène, Legendre, Paul, Luong Nguyen, Liem Binh, Marey, Jonathan, Morbieu, Caroline, Mouthon, Luc, Nguyen, Lee, Palmieri, Lola-Jade, Regent, Alexis, Szwebel, Tali-Anne, Terrier, Benjamin, Guerin, Corinne, Zerbit, Jérémie, Cheref, Kahina, Chitour, Kamil, Cisse, Mamadou Salif, Clarke, Ada, Clavere, Gaelle, Dusanter, Isabelle, Gaudefroy, Caroline, Jallouli, Moez, Kolta, Sami, Le Bourlout, Catherine, Marin, Nathalie, Menage, Nathalie, Moores, Alexandre, Peigney, Isabelle, Pierron, Cédric, Saleh-Mghir, Samira, Vallet, Mathilde, Michel, Marc, Melica, Giovanna, Lelievre, Jean-Daniel, Fois, Elena, Lim, Pascal, Matignon, Marie, Guillaud, Constance, Thiemele, Alaki, Schmitz, David, Bouhris, Marion, Belazouz, Syllia, Languille, Laetitia, Mekontso-Dessaps, Armand, Sadaoui, Thiziri, Mayaux, Julien, Cacoub, Patrice, Corvol, Jean-Christophe, Louapre, Céline, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aïcha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sébastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Lecronier, Marie, Beurton, Alexandra, Haudebourg, Luc, Deleris, Robin, Le Marec, Julien, Virolle, Sara, Nemlaghi, Safaa, Bureau, Côme, Mora, Pierre, De Sarcus, Martin, Clovet, Olivier, Duceau, Baptiste, Grisot, Paul Henri, Pari, Marie hélène, Arzoine, Jérémy, Clarac, Ulrich, Faure, Morgane, Delemazure, Julie, Decavele, Maxence, Morawiec, Elise, Demoule, Alexandre, Dres, Martin, Vautier, Mathieu, Allenbach, Yves, Benveniste, Olivier, Leroux, Gaelle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Cloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Gonçalo, Ferfar, Yasmina, Charbonnier, Fanny, Aguilar, Claire, Alby-Laurent, Fanny, Alyanakian, Marie-Alexandra, Bakouboula, Prissile, Broissand, Christine, Burger, Carole, Campos-Vega, Clara, Chavarot, Nathalie, Choupeaux, Laure, Elie, Caroline, Fournier, Benjamin, Granville, Sophie, Issorat, Elodie, Rouzaud, Claire, Vimpere, Damien, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Helene, Duclos-Vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Koumis, Ilias, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Chistophe, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El Amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Hélène, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Clan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Servettaz, Amélie, Deslée, Gaetan, Wynckel, Alain, Benoit, Philippe, Marquis, Eric, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Hélène, Mourad, Jean-Jacques, Sacco, Emmanuelle, Renet, Sophie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hopital Saint-Louis [AP-HP] (AP-HP), Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Centre de recherche en Myologie – U974 SU-INSERM, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CORIMUNO-19 Collaborative Group, Porcher, Raphaël, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), and ANR-21-COVR-0024,ACT-LONG-COVID,Caractérisation clinique et biologique du syndrome d'activation mastocytaire dans le COVID long et prédisposition génétique(2021)
Subjects: [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal Medicine
Abstract: International audience; Importance Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).Objective To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.Design, Setting, and Particpants This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.Interventions Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.Main Outcomes and Measures Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.Results Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).Conclusions and Relevance In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT04331808
Published: 2021
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14. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19 : a meta-analysis

Author: The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, [missing], Domingo, Pere, Mur, Isabel, Mateo, Gracia María, Gutierrez, Maria del Mar, Pomar, Virginia, de Benito, Natividad, Corbacho, Noemí, Herrera, Silvia, Millan, Lucia, Muñoz, Jessica, Malouf, Jorge, Molas, Maria Ema, Asensi, Victor, Horcajada, Juan Pablo, Estrada, Vicente, Gutierrez, Felix, Torres, Ferran, Perez-Molina, Jose A, Fortun, Jesús, Villar, Luisa M, Hohenthal, Ulla, Marttila, Harri, Vuorinen, Tytti, Nordberg, Marika, Valtonen, Mika, Frigault, Matthew J, Mansour, Michael K, Patel, Naomi J, Fernandes, Ana, Harvey, Liam, Foulkes, Andrea S, Healy, Brian C, Shah, Ruta, Bensaci, Ana Maria, Woolley, Ann E., Nikiforow, Sarah, Lin, Nina, Sagar, Manish, Shrager, Harry, Huckins, David S., Axelrod, Matthew, Pincus, Michael D, Fleisher, Jorge, Lampa, Jon, Nowak, Piotr, Vesterbacka, Jan C., Rasmuson, Johan, Skorup, Paul, Janols, Helena, Niward, Katarina F, Chatzidionysiou, Katerina, Asgeirsson, Hilmir, Parke, Åsa, Blennow, Ola, Svensson, Anna-Karin, Aleman, Soo, Sönnerborg, Anders, Henter, Jan-Inge, Horne, Anna Carin, Al-Beidh, Farah, Angus, Derek, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, Berry, Scott, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Cheng, Allen, Cove, Matt, De Jong, Menno, Derde, Lennie, Estcourt, Lise, Goossens, Herman, Gordon, Anthony, Green, Cameron, Haniffa, Rashan, Ichihara, Nao, Lamontagne, Francois, Lawler, Patrick, Litton, Ed, Marshall, John, McArthur, Colin, McAuley, Daniel, McGuinness, Shay, McVerry, Bryan, Montgommery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Reyes, Felipe, Rowan, Kathryn, Saito, Hiroki, Santos, Marlene, Seymour, Chris, Shankar-Hari, Manu, Turgeon, Alexis, Turner, Anne, van Bentum-Puijk, Wilma, van de Veerdonk, Frank, Webb, Steve, Zarychanski, Ryan, Baillie, J Kenneth, Beasley, Richard, Cooper, Nichola, Fowler, Robert, Galea, James, Hills, Thomas, King, Andrew, Morpeth, Susan, Netea, Mihai, Ogungbenro, Kayode, Pettila, Ville, Tong, Steve, Uyeki, Tim, Youngstein, Taryn, Higgins, Alisa, Lorenzi, Elizabeth, Berry, Lindsay, Salama, Carlos, Rosas, Ivan O., Ruiz-Antorán, Belén, Muñez Rubio, Elena, Ramos Martínez, Antonio, Campos Esteban, José, Avendaño Solá, Cristina, Pizov, Reuven, Sanz Sanz, Jesus, Abad-Santos, Francisco, Bautista-Hernández, Azucena, García-Fraile, Lucio, Barrios, Ana, Gutiérrez Liarte, Ángela, Alonso Pérez, Tamara, Rodríguez-García, Sebastian C, Mejía-Abril, Gina, Prieto, Jose Carlos, Leon, Rafael, VEIGA, VIVIANE C., SCHEINBERG, PHILLIP, FARIAS, DANIELLE L.C., PRATS, JOÃO G., CAVALCANTI, ALEXANDRE B., MACHADO, FLAVIA R., ROSA, REGIS G., BERWANGER, OTÁVIO, AZEVEDO, LUCIANO C.P., LOPES, RENATO D., DOURADO, LETICIA K., CASTRO, CLAUDIO G., ZAMPIERI, FERNANDO G., AVEZUM, ALVARO, LISBOA, THIAGO C., ROJAS, SALOMÓN S.O., COELHO, JULIANA C., LEITE, RODRIGO T., CARVALHO, JULIO CESAR, ANDRADE, LUIS E.C., SANDES, ALEX R., PINTÃO, MARIA CAROLINA T., SANTOS, SUELI V., ALMEIDA, THIAGO M.L., COSTA, ANDRÉ N., GEBARA, OTAVIO C.E., FREITAS, FLAVIO G.R., PACHECO, EDUARDO S., MACHADO, DAVID J.B., MARTIN, JOSIANE, CONCEIÇÃO, FABIO G., SIQUEIRA, SUELLEN R.R., DAMIANI, LUCAS P., ISHIHARA, LUCIANA M., SCHNEIDER, DANIEL, DE SOUZA, DENISE, Hermine, Olivier, Mariette, Xavier, Tharaux, Pierre Louis, Resche Rigon, Matthieu, Porcher, Raphael, Ravaud, Philippe, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Tibi, Annick, Yazdanpanah, Yazdan, Dougados, Maxime, Bureau, Serge, Horby, Peter W, Landray, Martin J, Baillie, Kenneth J, Buch, Maya H, Chappell, Lucy C, Day, Jeremy N, Faust, Saul N, Haynes, Richard, Jaki, Thomas, Jeffery, Katie, Juszczak, Edmund, Lim, Wei Shen, Mafham, Marion, Montgomery, Alan, Mumford, Andrew, Thwaites, Guy, Kamarulzaman, Adeeba, Syed Omar, Sharifah Faridah, Ponnampalavanar, Sasheela, Raja Azwa, Raja Iskandar Syah, Wong, Pui Li, Kukreja, Anjanna, Ong, Hang Cheng, Sulaiman, Helmi, Basri, Sazali, Ng, Rong Xiang, Megat Johari, Bushra, Rajasuriar, Reena, Chong, Meng Li, Neelamegam, Malinee, Syed Mansor, Syed Mukhtar, Zulhaimi, Nurul Syuhada, Lee, Cheng Siang, Altice, Frederick, Price, Christina, Malinis, Maricar, Hasan, Mohd Shahnaz, Wong, Chee Kuan, Chidambaram, Suresh, Misnan, Nor Arisah, Mohd Thabit, Alif Adlan, Sim, Benedict, Bidin, Farah Nadiah, Mohd Abd Rahim, Mohd Abd Hafiz, Saravanamuttu, Sujana, Tuang, Wei Xuan, Mohamed Gani, Yasmin, Thangavelu, Suvintheran, Tay, Kim Heng, Ibrahim, Nur Munirah, Halid, Luqman Alhakim, Tan, Kok Tong, Mukri, Mohd Noor Azreet, Arip, Masita, Koh, Hui Moon, Syed Badaruddin, Syarifah Nurul Ain, Raja Sureja, Letchumi, Chun, Geok Ying, TORRE-CISNEROS, JULIAN, MERCHANTE, NICOLAS, LEON, RAFAEL, CARCEL, SHEILA, GARRIDO, JOSE CARLOS, Galun, Eitan, Soriano, Alex, Martínez, José Antonio, Castán, Clara, Paredes, Roger, Dalmau, David, Carbonell, Cristina, Espinosa, Gerard, Castro, Pedro, Muñóz, José, Almuedo, Alex, Prieto, Sergio, Pacheco, Iván, Ratain, Mark, Pisano, Jennifer, Strek, Mary, Adegunsoye, Ayodeji, Karrison, Theodore, Declercq, Jozefien, Van Damme, Karel, De Leeuw, Elisabeth, Bosteels, Cedric, Maes, Bastiaan, Vale, Claire L., Godolphin, Peter J., Fisher, David, Higgins, Julian P. T., Spiga, Francesca, Savovic, Jelena, Tierney, Jayne, Baron, Gabriel, Benbenishty, Julie S., Berry, Lindsay R., Broman, Niklas, Cavalcanti, Alexandre Biasi, Colman, Roos, De Buyser, Stefanie, Derde, Lennie P. G., Omar, Sharifah Faridah, Fernandez-Cruz, Ana, Feuth, Thijs, Garcia, Felipe, Garcia-Vicuna, Rosario, Gonzalez-Alvaro, Isidoro, Gordon, Anthony C., Horby, Peter W., Horick, Nora K., Kumar, Kuldeep, Lambrecht, Bart, Landray, Martin J., Leal, Lorna, Lederer, David J., Merchante, Nicolas, Mohan, Shalini V., Nivens, Michael C., Oksi, Jarmo, Perez-Molina, Jose A., Postma, Simone, Ramanan, Athimalaipet V., Reid, Pankti D., Rutgers, Abraham, Sancho-Lopez, Aranzazu, Seto, Todd B., Sivapalasingam, Sumathi, Soin, Arvinder Singh, Staplin, Natalie, Stone, John H., Strohbehn, Garth W., Sunden-Cullberg, Jonas, Torre-Cisneros, Julian, Tsai, Larry W., van Hoogstraten, Hubert, van Meerten, Tom, Veiga, Viviane Cordeiro, Westerweel, Peter E., Diaz, Janet V., Marshall, John C., Sterne, Jonathan A. C., Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL), World Health Organization, and Group, WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working
Subjects: Male, medicine.medical_specialty, Randomization, Secondary infection, Placebo, Antibodies, Monoclonal, Humanized, Internal medicine, Cause of Death, Medicine and Health Sciences, Medicine, Humans, Prospective Studies, Prospective cohort study, Glucocorticoids, METAANALYSIS, Cause of death, Aged, Randomized Controlled Trials as Topic, business.industry, Coinfection, Interleukin-6, COVID-19, Odds ratio, General Medicine, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Hospitalization, Meta-analysis, Disease Progression, Drug Therapy, Combination, Female, business
Abstract: [Importance] Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm., [Objective] To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes., [Data Sources] Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts., [Study Selection] Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria., [Data Extraction and Synthesis] In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality., [Main Outcomes and Measures] The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days., [Results] A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P, [Conclusions and Relevance] In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality., [Trial Registration] PROSPERO Identifier: CRD42021230155., Funding for administrative and communications support was provided by the World Health Organization.
Published: 2021

15. French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides)

Author: Terrier, Benjamin, Darbon, Raphaël, Durel, Cécile-Audrey, Hachulla, Eric, Karras, Alexandre, Maillard, Hélène, Papo, Thomas, Puechal, Xavier, Pugnet, Grégory, Quemeneur, Thomas, Samson, Maxime, Taille, Camille, Guillevin, Loïc, Audard, Vincent, Aumaître, Olivier, Briot, Karine, Cacoub, Patrice, Cathebras, Pascal, Chauveau, Dominique, Chosidow, Olivier, Chouchana, Laurent, Cottin, Vincent, Cornec, Divi, Daugas, Eric, Diot, Elisabeth, Dupin, Nicolas, El Karoui, Khalil, Fain, Olivier, Gobert, Pierre, Guilpain, Philippe, Hamidou, Mohamed, Hummel, Aurelie, Jachiet, Marie, Jouneau, Stephane, Jourde-Chiche, Noémie, Landron, Cédric, Le Jeunne, Claire, Lega, Jean-Christophe, Mariette, Xavier, Morel, Nathalie, Pagnoux, Christian, Remy, Philippe, Vandergheynst, Frederic, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Association France Vascularites [Paris], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Toulouse [Toulouse], Centre hospitalier [Valenciennes, Nord], Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Pediatrics, medicine.medical_specialty, lcsh:Medicine, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Disease, Churg-Strauss Syndrome, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Eosinophilic, Necrotizing Vasculitis, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Position Statement, Genetics (clinical), 030203 arthritis & rheumatology, Polyarteritis nodosa, business.industry, lcsh:R, Granulomatosis with Polyangiitis, General Medicine, medicine.disease, 3. Good health, Polyarteritis Nodosa, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Quality of Life, Granulomatosis with polyangiitis, business, Microscopic polyangiitis, Vasculitis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3–6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12–48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.
Published: 2020

16. SARS-CoV-2 infection in patients with primary Sjögren syndrome: characterization and outcomes of 51 patients

Author: Brito-Zerón, Pilar, Melchor, Sheila, Seror, Raphaèle, Priori, Roberta, Solans, Roser, Kostov, Belchin, Baldini, Chiara, Carubbi, Francesco, Callejas, Jose Luis, Guisado-Vasco, Pablo, Hernández-Molina, Gabriela, Pasoto, Sandra G, Valim, Valeria, Sisó-Almirall, Antoni, Mariette, Xavier, Carreira, Patricia, Ramos-Casals, Manuel, Brito-Zerón, P, Morcillo, C, Flores-Chávez, A, Ramos-Casals, M, Acar-Denizli, N, Horvath, I F, Szanto, A, Tarr, T, Seror, R, Mariette, X, Mandl, T, Olsson, P, Li, X, Xu, B, Baldini, C, Bombardieri, S, Gottenberg, J E, Gandolfo, S, De Vita, S, Priori, R, Giardina, F, Hernandez-Molina, G, Sánchez-Guerrero, J, Kruize, A A, Hinrichs, A, Valim, V, Isenberg, D, Solans, R, Rischmueller, M, Downie-Doyle, S, Kwok, S-K, Park, S-H, Nordmark, G, Suzuki, Y, Kawano, M, Giacomelli, R, Devauchelle-Pensec, V, Saraux, A, Hofauer, B, Knopf, A, Bootsma, H, Vissink, A, Morel, J, Vollenveider, C, Atzeni, F, Retamozo, S, Moça Trevisano, V, Armagan, B, Kilic, L, Kalyoncu, U, Pasoto, S G, Kostov, B, Sisó-Almirall, A, Consani-Fernández, S, Carubbi, F, Callejas, J L, López-Dupla, M, Pérez-Alvarez, R, Akasbi, M, Guisado-Vasco, P, Sánchez, I, Hospital Universitario 12 de Octubre [Madrid], EULAR standing committee of People with Arthritis/Rheumatism in Europe (PARE), H. CIMA-Sanitas, Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Instituto Mexicano del Seguro Social [Mexico City, Mexico] (IMSS), Universidad de Colima [Mexico], Hospital Clinic [Barcelona, Spain], İstanbul Üniversitesi, İstanbul, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary, MTA-Debreceni Egyetem, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Skåne University Hospital [Malmö, Suède], Stockholm University, Wuhan University [China], Pisa University Hospital, Nuclear Medicine Unit, Humanitas Gavazzeni, Bergamo, Italy, University Hospitals, Strasbourg, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Federal University of Espírito Santo, University Hospital Vall d’Hebròn [Barcelona, Spain], Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigaciones Biomèdiques August Pi i Sunye (IDIBAPS), Università degli studi di Palermo - University of Palermo, Hospitales Universitarios de Granada/Universidad de Granada, Hospital Universitario Quironsalud, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Rheumatology Unit, Department of Internal Medicine, University of Palermo, Palermo, Italy, and Michel, Geneviève
Subjects: Male, medicine.medical_specialty, Multivariate analysis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Comorbidity, Laboratory abnormality, comorbidities, outcomes, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Risk Factors, Internal medicine, medicine, Humans, In patient, Pharmacology (medical), 030212 general & internal medicine, Registries, Risk factor, Primary Sjögren Syndrome, AcademicSubjects/MED00360, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, Primary SS, SARS-Cov-2, Middle Aged, medicine.disease, 3. Good health, Hospitalization, Sjogren's Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, Female, business
Abstract: Objective To analyse the prognosis and outcomes of SARS-CoV-2 infection in patients with primary SS. Methods We searched for patients with primary SS presenting with SARS-CoV-2 infection (defined following and according to the European Centre for Disease Prevention and Control guidelines) among those included in the Big Data Sjögren Registry, an international, multicentre registry of patients diagnosed according to the 2002/2016 classification criteria. Results A total of 51 patients were included in the study (46 women, mean age at diagnosis of infection of 60 years). According to the number of patients with primary SS evaluated in the Registry (n = 8211), the estimated frequency of SARS-CoV-2 infection was 0.62% (95% CI 0.44, 0.80). All but two presented with symptoms suggestive of COVID-19, including fever (82%), cough (57%), dyspnoea (39%), fatigue/myalgias (27%) and diarrhoea (24%), and the most frequent abnormalities included raised lactate dehydrogenase (LDH) (88%), CRP (81%) and D-dimer (82%) values, and lymphopenia (70%). Infection was managed at home in 26 (51%) cases and 25 (49%) required hospitalization (five required admission to ICU, four died). Compared with patients managed at home, those requiring hospitalization had higher odds of having lymphopenia as laboratory abnormality (adjusted OR 21.22, 95% CI 2.39, 524.09). Patients with comorbidities had an older age (adjusted OR 1.05, 95% CI 1.00, 1.11) and showed a risk for hospital admission six times higher than those without (adjusted OR 6.01, 95% CI 1.72, 23.51) in the multivariate analysis. Conclusion Baseline comorbidities were a key risk factor for a more complicated COVID-19 in patients with primary SS, with higher rates of hospitalization and poor outcomes in comparison with patients without comorbidities.
Published: 2020

17. Atteinte rénale au cours du syndrome de Sjögren 

Author: Mariette, Xavier, Francois, Hélène, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Acidose tubulaire distale, Tubulo-interstitial nephritis, Glomérulonéphrite membrano-proliférative, Cryoglobulinemia, Primary Sjögren syndrome, Distal tubular acidosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Néphrite tubulo-interstitielle, Membranoproliferative glomerulonephritis, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cryoglobulinémie, Syndrome de Sjögren primitif
Abstract: International audience; Primary Sjögren syndrome is an autoimmune disorder characterized by lymphoplasmacytic infiltration of the exocrine (salivary and lachrymal) glands resulting in sicca symptoms (dryness). Systemic complications can occur in primary Sjögren syndrome, but renal involvement is rare, affecting < 10% patients. The most frequent form of nephropathy in primary Sjögren syndrome is tubulointerstitial nephritis, where infiltration of the kidney by plasma cells is a key feature and shows similarity to the lymphoplasmacytic infiltration of the salivary glands. Electrolyte disturbances may occur in primary Sjögren syndrome, such as renal distal tubular acidosis, diabetes insipidus, Gitelman syndrome, or Fanconi syndrome. Glomerular involvement is less frequently detected in patients with primary Sjögren syndrome, but can take the form of membranoproliferative glomerulonephritis secondary to cryoglobulinaemia. The renal prognosis in patients with primary Sjögren syndrome and TIN or glomerular disease is usually good, but the risk of chronic kidney disease remains significant for some patients. Appropriate screening must be performed at least once a year in patients with systemic primary Sjögren syndrome in order to facilitate the early detection of renal complications. In this Review, we discuss the epidemiology, pathophysiology, differential diagnosis, and treatment of renal disease in primary Sjögren syndrome.; Le syndrome de Sjögren primitif est une maladie auto-immune caractérisée par une infiltration lymphoplasmocytaire des glandes exocrines (salivaires et lacrymales) entraînant le symptôme cardinal, qui est un syndrome sec buccal et oculaire. Les complications systémiques sont possibles, mais l’atteinte rénale est rare et affecte en général moins de 10 % des patients. L’atteinte rénale la plus spécifique et fréquente du syndrome de Sjögren primitif est la néphrite tubulo-interstitielle au cours de laquelle l’interstitium est infiltré par des lymphocytes et des plasmocytes de façon similaire à ce qui est observé dans les glandes exocrines. Des troubles hydroélectrolytiques peuvent survenir comme l’acidose tubulaire distale, le diabète insipide, le syndrome de Gitelman ou de Fanconi. L’atteinte glomérulaire est moins fréquente et correspond à une glomérulonéphrite membrano-proliférative secondaire à la cryoglobulinémie, qui est une complication classique du syndrome de Sjögren primitif. Le pronostic rénal des patients ayant une néphrite tubulo-interstitielle est en général favorable, mais le risque d’insuffisance rénale chronique reste élevé. Il est donc important que la néphrite tubulo-interstitielle soit dépistée tous les ans chez les patients ayant un syndrome de Sjögren primitif avec atteinte systémique. Nous abordons ici l’épidémiologie, la physiopathologie, les diagnostics différentiels et le traitement des atteintes rénales spécifiques au cours du syndrome de Sjögren primitif.
Published: 2020

18. Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

Author: Victor Judith, Devaux Mathilde, Corre Clémence, Morin Franck, Ebstein Esther, Desmurs Marie, Juillard Laurent, Descamps Elise, Galland Joris, Gahier Penhoat Mélanie, Hellier Jean-Pierre, Mariette Xavier, Poix Elsa, Hudry Christophe, Constant Elodie, Trijau Sophie, Moranne Olivier, Diot Elisabeth, Hie Miguel, Guilpain Philippe, Boussoualim Karima, Mathian Alexis, Pouchot Jacques, Rohmer Julien, Senet Patricia, Michaud Martin, Tieulie Nathalie, Liote Frédéric, Ducornet Angélique, Couret Marie, Revuz Sabine, Morel Hugo, Moly Marie, Direz Guillaume, Milesi-Lecat Anne-Marie, Meinzer Ulrich, Bader-Meunier Brigitte, Steib Sarah, Gauthier-Prieur Maud, Bertolini Ewa, Gombert Bruno, Dumel Anne-Elisabeth, Henriot Basile, Froissart Antoine, Smets Perrine, Robin Sophie, Rousselin Clémentine, Moulinier Laurence, Mazet-Guillaume Betty, Brondino Regine, Malochet-Guinamand Sandrine, Balandraud Nathalie, Gibert Christelle, Godeau Bertrand, Aeschlimann Florence, Bonnet Christine, Plassard Samira, Lebrun Agnès, Mehsen-Cetre Nadia, Arlet Jean-Benoît, Gagneux-Lemoussu Laurence, Kemiche Farid, Michon Mathilde, Szafors Paulina, Werle Claude, Guillaud Constance, La Batide Alanore Sylvain, Borie Raphaël, Chazerain Pascal, Puyraimond-Zemmour Déborah, Barrelet Audre, Bach-Bunner Maxime, Flaisler Françoise, Euvrard Romain, Evon Philippe, Feurer Elodie, Gerard Nathalie, Gervais Elisabeth, Sordet Christelle, Bally Stéphane, Mazouyez Arnaud Angers, Guillot Xavier, Comarmond Chloé, Leloire Olivier, Fauconier Marion, Bouhour Françoise, Woessner Juliette, Jaccard Clara, Langlois Vincent, Sicaud Aurélie, Rolland Michel, Kabala Anna, Atlan Lucie, Amador-Borreiro Blanca, Jan Catherine, Leturcq Tifenn, Gonnet-Gracia Camille, Lanot Sylvain, Hachulla Eric, Bonidan Olivier, Domont Fanny, Dumaine Cécile, Bouiller Kévin, Senbel Eric, Comparon Céline, Huguenel Serge, Despaux Jacques, Roth Olivier, Berthoux Emilie, Dehimat Sarahe, Costedoat-Chalumeau Nathalie, Bayer Guillaume, Melki Isabelle, Toussirot Eric, Buchlin Pierre, Baumier Vincent, Charcot Agnès, Durand Géraldine, Garraud Thomas, Richez Christophe, Gillard Jérôme, Chaigne Benjamin, Rousiere Mickaël, Le Guen Guegan Sophie, Chertok Pascale, Lucas Virginie, Sadji Fatiha, Garnier Nicole, Sailler Laurent, Garrot Jean-François, Taffignon-Clave Séverine, Charles Pierre, Bernoux-Manat Brigitte, Salliot Carine, Fechtenbaum Jacques, Quenet Marion, Le Guenno Guillaume, Lanteri Aurélia, Hermet Marion, Delahousse Michel, Basch André, Grateau Gilles, Chevalier Xavier, Nocturne Gaétane, Schmidt Jean, Pacaud-Vitoux Isabelle, Roumier Mathilde, Rozenberg Sylvie, Veillard Eric, Roux Nicolas, Marhadour Thierry, Colette-Cedoz Marie-Eve, Cohen Gregory, Foltz Violaine, Fouque-Aubert Anne, Havard Marie-Noelle, Molto Anna, Chevreau Maxime, Strotz Victor, Allanore Yannick, Grardel Bruno, Francois-Pradier Hélène, Devauchelle-Pensec Valérie, Hennequin Pascal, Warzocha Ursula, Collercandy Nived, Bayle Sophie, Audren Victor, Virone Alexandre, Bennet Pascal, Grados Franck, Charpin Caroline, Fuzibet Piera, Albert Jean-David, Larbre Jean-Paul, Coutarel Cécile, Nicolas-Vullierme Sabine, Gastaldi Romain, Guyot Marie-Hélène, Georgescu Dana, Clavel Gaëlle, Tison Alice, Viallard Jean-François, Maria Alexandre, Glanowski Camille, Leroux Christophe, Vidon Mathias, Banal Frédéric, Fulpin Jean, Chotard Emilie, Gaud-Listrat Véronique, Jean Sylvie, Seguier Julie, Jacquemier Jean-Michel, Chatelus Emmanuel, Djeddi Djamal-Dine, Contamine-Sur-Arve Mazyad Hassan, Georgin-Lavialle Sophie, Belot Alexandre, Seve Pascal, Willems Alexandra, Moulis Guillaume, Latourte Augustin, Roux Marielle, Bolla Gilles, Renard Myriam, Xerri-Campano Bernadette, Bisson-Vaivre Aurélia, Fichet Amandine, Dufauret-Lombard Carine, Nielly Hubert, Ledoult Emmanuel, Alcais Didier, Giraudet-Le Quintrec Jeanine-Sophie, Wendling Daniel, Govindaraju-Audouard Sophie, Claudepierre Pascal, Fritz Pierre, Fougerousse Anne-Claire, Marotte Hubert, Fabre Sylvie, Banneville Béatrice, Quartier-Dit-Maire Pierre, Juge Pierre-Antoine, Moura Bertrand, Maillet Thibault, Messer Laurent, Thomachot Benoît, Giraud-Morelet Aude, Sparsa Lætitia, Kabchou Abdelkrim, Grasland Anne, Maurier François, Belin Véronique, Grenoble Gimonnet Pauline, Balblanc Jean-Charles, Andre Emma, Veillard Ericveillard Marie-Eliseeric, Chu Miow Lin, Pugnet Grégory, Wisniewski Michel, Carbasse Aurélia, Rene Jessica, Economu-Dubosc Andra, Bouldoires Bastien, Glace Baptiste, Benhamou Mathilde, Legoupil Nathalie, Morel Jacques, Castel Brice, Lafforgue Pierre, Carteni Maurizio, Lohse Anne, Detree Frédérick, Celant Annalisa, Trefond Ludovic, Maillard Hélène, Remy Philippe, Barnetche Thomas, Servettaz Amélie, Vigne Camille, Ferreira-Maldent Nicole, Mangon Quentin, Keraen Jérémy, Fautrel Bruno, Frantzen Léa, Legrand Erick, Sellam Jérémie, Tenenbaum Nora, Sene Thomas, Duc Catherine, Bouvard Eric, Dieudonne Yannick, Ollagnon Henri-Olivier, Deslandre Chantal, Gury Aline, Desplats Marie, Karman Françoise, Drouet Béatrice, Vidon Claire, Kone-Paut Isabelle, Groza Monica, Jamard Bénédicte, Parrot Antoine, Vial Guillaume, Ebbo Mikaël, Ait-Abdallah Nassim, Veillon Laurent, Roriz Mélanie, Chaillous Benoît, Rouidi Sid-Ahmed, Sobanski Vincent, Poulet Antoine, Clavel-Osorio Cyril, Nguyen Minh, Felten Renaud, Goulenok Tiphaine, Audoin-Pajot Christine, Foret Jennifer, Arniaud Denis, Benammar Mohammed, Boudou Laurence, Pascaud-Mansour Yasmina, Pavy Stephan, Sornay-Rendu Elisabeth, Pascart Tristan, Madelon Aurélie, Koreichi Abdeldajallil, Flipo René-Marc, El Mahou Soumaya, Benmansour Ahmed, Arty-Hue Herliette, Pers Yves-Marie, Hittinger-Roux Ambre, Sacco Isabelle, Fernandes Fanny, Gandjbakhch Frédérique, Maury Frédéric, Hacquard-Bouder Cécile, Foutrier-Morello Catherine, Rossi Linda, Belkhir Rakiba, Riviere Etienne, Drumez Elodie, Avouac Jérôme, Benainous Ruben, Champy Romuald, Florens Nans, Pichon Maud, Gibert Eric, Benhamou Ygal, Portier Agnès, Riviere Sébastien, Pham Thao, Blaison Gilles, Colombey Antoine, Marchou-Lopez Sylvie, Roux Fabienne, Leroy Rémi, Lejeune Charlotte, Bacquet-Deschryver Hélène, Romier Mélanie, Simoens Justine, Caumont Hervé, Arnaud Laurent, Paulin Lætitia, Duret Pierre-Marie, Dieude Philippe, Coury-Lucas Fabienne, Pha Micheline, Herasse Muriel, Mahevas Matthieu, Roitg Isabelle, Karkowski Ludovic, Dhote Robin, Chaudier Bernard, Gourmelen Olivier, Trouillier Sébastien, Henry Julien, Daver-Malaterre Laurence, Cathebras Pascal, Goupille Philippe, Seror Raphaële, Thomas Thierry, Pertuiset Edouard, Amoura Zahir, Richard-Colmant Gaëlle, Souchaud-Debouverie Odile, Lahalle Sophie, Jouvray Mathieu, Hentgen Véronique, Courvoisier Natacha, Charlot-Lambrecht Isabelle, Damade Richard, Argenteuil Pizana Gabrielle, Fontanges Elisabeth, Morel Gautier, Roux Christian, Perard Laurent, Gaches Francis, Cacoub Patrice, Mekinian Arsène, Cohen Fleur, Margarit Nathalie, Salmon Jean-Hugues, Guillaume Séverine, Gilson Mélanie, Coutier Fabrice, Rouzaud Diane, Duhamel Alain, Combe Bernard, Jullien Denis, Gill Ghislaine, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Saint-Joseph [Marseille], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPCité Médecine Paris Centre), Université Paris Cité (UPCité), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Necker - Enfants Malades [AP-HP], CH Belfort-Montbéliard, Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Avicenne [AP-HP], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de rééducation et de réadaptation de l'appareil locomoteur et des pathologies du rachis [CHU Cochin], CHU Rouen, Normandie Université (NU), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Médecine interne [Hôpitaux civils de Colmar], Hôpitaux Civils de Colmar, Institut national de recherches archéologiques préventives (Inrap), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Cochin [AP-HP], PSA Peugeot Citroën (PSA), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Hôpital d'Instruction des Armées Laveran, Service de rhumatologie [Groupe Hospitalier Diaconesses Croix Saint Simon], Groupe Hospitalier Diaconesses Croix Saint-Simon, Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation Ophtalmologique Adolphe de Rotschild, Service de Médecine Intensive et Réanimation [Tours], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST, Hôpital Foch [Suresnes], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), Service de médecine interne [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de rhumatologie (Hôpitaux Civils de Colmar), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de rhumatologie [CH Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Chimie Agro-Industrielle (CAI), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'immuno-rhumatologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, CHU Trousseau [Tours], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier de Dax, Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Joseph Ducuing - Varsovie [Toulouse] (HJD), Hôpitaux Privés de Metz (HPMetz), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de médecine interne [Centre hospitalier Lons le Saunier], Centre hospitalier Lons le Saunier, Service de Rhumatologie [CHU de Grenoble], Hôpital Sud de Grenoble, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital saint louis (LA ROCHELLE - Hôpital Saint Louis), CH La Rochelle, Service de Médecine Interne [AP-HP, CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], CHU Trousseau [APHP], CHU Amiens-Picardie, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Langues et civilisations à tradition orale (LACITO), Université Sorbonne Nouvelle - Paris 3-Institut National des Langues et Civilisations Orientales (Inalco)-Centre National de la Recherche Scientifique (CNRS), Études Pharmaco-Immunologie (EPI), Université de La Réunion (UR), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique-Hôpitaux de Paris - Espace éthique (AP-HP Espace éthique), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, CHU Toulouse [Toulouse], Département de Pédiatrie [Rennes] = Paediatrics [Rennes], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Club Rhumatismes et Inflammation, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Arthrites autoimmunes (AA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Alençon-Mamers (CHICAM), Service de Médecine interne [CH Antibes Juan-Les-Pins], Centre Hospitalier d’Antibes Juan-les-Pins (CH Antibes Juan-Les-Pins), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), CHU Clermont-Ferrand, Université de Lille, Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA), Centre Hospitalier Victor Jousselin de Dreux, Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier de Belfort (Service de Rhumatologie), Oncology, Regional Hospital of Orleans, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Gabriel Montpied [Clermont-Ferrand], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, CHU Saint-Etienne, Paediatrics, Paediatric Internal Medicine, Rheumatology and Infectious Diseases [Paris], Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Rhumatologie [CHRU Montpellier], Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Histoire, Archéologie et Littératures des mondes chrétiens et musulmans médiévaux (CIHAM), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-École des hautes études en sciences sociales (EHESS)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Columbia University Irving Medical Center (CUIMC), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, Assistance Publique - Hôpitaux de Marseille (APHM)-Institut du Mouvement et de l'appareil Locomoteur (IML), Service d'Anesthésie réanimation [CHU Tenon], Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Hopital Réné Dubos, Laboratoire d'Economie de Dauphine (LEDa), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine interne - hôpital européen Georges-Pompidou, Aix Marseille Université (AMU), Sorbonne Université (SU), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de La Réunion - Faculté de Lettres et Sciences humaines (UR FLSH), Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Grenoble Alpes - École supérieure du professorat et de l'éducation - Académie de Grenoble (UGA ESPE Grenoble), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Groupe ENergie Electrique et SYStémique (LAPLACE-GENESYS), LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cabinet Médical de Rhumatologie, Marseille, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de dermatologie et allergologie [CHU Tenon], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier de Mulhouse (Service de Rhumatologie), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), FHU 'Integrated center for research in inflammatory diseases - InCREASe', Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Saint-André, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Joseph Ducuing, Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire Navier (NAVIER UMR 8205), École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques (ENSIACET), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV]Life Sciences [q-bio], communicable diseases, Disease, Logistic regression, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, law, Adrenal Cortex Hormones, Epidemiology, Immunology and Allergy, Medicine, 030212 general & internal medicine, 2. Zero hunger, education.field_of_study, glucocorticoids, Mortality rate, tumor necrosis factors, Intensive care unit, 3. Good health, Hospitalization, Autoinflammatory Disorders, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biological therapy, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hypertension, Female, Adult, medicine.medical_specialty, Immunology, Population, imported, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Internal medicine, Rheumatic Diseases, Humans, autoimmune diseases, Obesity, education, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, business, Body mass index
Abstract: ObjectivesThere is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.MethodsIndividuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate–severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.ResultsOf 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05–1.10), female gender (OR=0.45, 95% CI: 0.25–0.80), body mass index (OR=1.07, 95% CI: 1.02–1.12), hypertension (OR=1.86, 95% CI: 1.01–3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09–3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47–29.62) and rituximab (OR=4.21, 95% CI: 1.61–10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87–2.42) (n=175 each group).ConclusionsIn the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD.Trial registration numberClinicalTrials.gov Registry (NCT04353609).
Published: 2020

19. Additional file 1 of Assessing the effect of genetic markers on drug immunogenicity from a mechanistic model-based approach

Author: Duhazé, Julianne, Caubet, Miguel, Hässler, Signe, Bachelet, Delphine, Allez, Matthieu, Deisenhammer, Florian, Fogdell-Hahn, Anna, Gleizes, Aude, Hacein-Bey-Abina, Salima, Mariette, Xavier, Pallardy, Marc, and Broët, Philippe
Abstract: Additional file 1 Supplementary material.
Published: 2020
Full Text: View/download PDF

20. Additional file 1 of Seasonal effect on fatigue, pain and dryness in primary Sjögren’s syndrome

Author: Pierre-Marie Duret, Meyer, Nicolas, Saraux, Alain, Devauchelle-Pensec, Valérie, Raphaele Seror, Le-Guern, Véronique, Larroche, Claire, Aleth Perdriger, Sibilia, Jean, Guardiolle, Vianney, Mariette, Xavier, and Jacques-Eric Gottenberg
Subjects: stomatognathic diseases, human activities, humanities, eye diseases
Abstract: Additional file 1: Table S1. Drug regimens used at enrolment in the ASSESS cohort and number of patients with systemic immuno-modulatory drugs and symptomatic treatments of dryness. Table S2. Influence of seasons on objective assessments of ocular and oral dryness (Schirmer test ≤5 mm; Salivary flow ≤0.1 mL/min). Table S3. Variations of pain, fatigue and dryness VASs (on a 100-unit scale) and of the ESSPRI score according to seasons, adjusted on age, immunosuppressive treatments and symptomatic treatments of dryness.
Published: 2020
Full Text: View/download PDF

21. Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Author: Tarn, Jessica R, Howard-Tripp, Nadia, Lendrem, Dennis W, Mariette, Xavier, Saraux, Alain, Devauchelle-Pensec, Valerie, Seror, Raphaele, Skelton, Andrew J, James, Katherine, McMeekin, Peter, Al-Ali, Shereen, Hackett, Kate, Lendrem, B Clare, Hargreaves, Ben, Casement, John, Mitchell, Sheryl, Bowman, Simon J, Price, Elizabeth, Pease, Colin T, Emery, Paul, Lanyon, Peter, Hunter, John, Gupta, Monica, Bombardieri, Michele, Sutcliffe, Nurhan, Pitzalis, Costantino, McLaren, John, Cooper, Annie, Regan, Marian, Giles, Ian, Isenberg, David, Saravanan, Vadivelu, Coady, David, Dasgupta, Bhaskar, McHugh, Neil, Young-Min, Steven, Moots, Robert, Gendi, Nagui, Akil, Mohammed, Griffiths, Bridget, Johnsen, Svein J A, Norheim, Katrine B, Omdal, Roald, Stocken, Deborah, Everett, Colin, Fernandez, Catherine, Isaacs, John D, Gottenberg, Jacques-Eric, Ng, Wan-Fai, Dieude, Philippe, Dubost, Jean Jacques, Fauchais, Anne-Laure, Goeb, Vincent, Hachulla, Eric, Larroche, Claire, Le Guern, Véronique, Morel, Jacques, Perdriger, Aleth, Puéchal, Xavier, Rist, Stephanie, Sen, Damien, Sibilia, Jean, Vittecoq, Olivier, Benessiano, Joelle, Tubiana, Sarah, Inamo, Karine, Gaete, Stanie, Batouche, Djilali, Molinari, Domitille, Randrianandrasana, Mickael, Pane, Isabelle, Abbe, Adeline, Baron, Gabriel, Ravaud, Philippe, Dubost, Jean-Jacques, Rist, Stéphanie, Devauchelle-Pensec, Valérie, Hayem, Gilles, Hatron, Pierre, Sene, Damien, Zarnitsky, Charles, Furlan, Valérie, Perrodeau, Elodie, Brown, S, Navarro, N Coy, Pitzalis, C, Emery, P, Pavitt, S, Gray, J, Hulme, C, Hall, F, Busch, R, Smith, P, Dawson, L, Bombardieri, M, Ng, W-F, Pease, C, Price, E, Sutcliffe, N, Woods, C, Ruddock, S, Everett, C, Reynolds, C, Skinner, E, Poveda-Gallego, A, Rout, J, Macleod, I, Rauz, S, Bowman, S, Hall, Frances, Bacaba, Elalaine C, Frankland, Helen, Chadravarty, Kuntal, Lamabadusuriya, Shamin, Pitzalis, Constantino, Breston, Celia, Culfear, Karen, Riddell, Claire, Hamburger, John, Richards, Andrea, Rauz, Saaeh, Brailsford, Sue, Dasgin, Joanne, Logan, Joanne, Mulherin, Diarmuid, Andrews, Jacqueline, Emery, Pau, McManus, Alison, Pease, Colin, Pickles, David, Booth, Alison, Kin, Jon King, Holt, Amanda, Dimitroulas, Theodoros, Kadiki, Lucy, Kaur, Daljit, Kitas, George, Khan, Abdul, Cosier, Tracey, Panthakalam, Mintrim, Kell, Lloyd, Mark, Moore, Lisa, Gordon, Esther, Lawson, Cathy, Stirton, Lesley, Ortiz, Gill, Pelger, Suzannah, Gorman, Claire, Hans, Balinder, Clunie, Gavin, Lane, Suzanne, Rose, Ginny, Cuckow, Sue, Batley, Michael, Einosas, Ruby, Knight, Susan, Symmons, Deborah, Jones, Beverley, Carr, Andrew, Edgar, Suzanne, Figuereido, Francisco, Foggo, Heather, Lendrem, Dennis, Macleod, Iain, Downie, Christine, Tarn, Jessica, Locke, James, Legg, Sarah, Mirza, Kamran, Hetherington, Laura, Jones, Adrian, Muir, Alice, White, Paula, Pugmire, Susan, Vadivelu, Saravanan, Watkins, Marianne, Field, Anne, Kaye, Stephen, Mewar, Devesh, Medcalf, Patricia, Tomlinson, Pamela, Whiteside, Debbie, Pauling, John, James, Julie, Dowden, Andrea, McDermott, Jayne, Godia, Olivia, Kidd, Elizabeth, Palmer, Lynne, Li, Charles, Bartrum, Sarah, Mead, De, Katsande, Victoria, Long, Pamela, Vermaak, Erin, Turner, Janet, Chandra, Usha, MacKay, Kirsten, Fedele, Stefano, Ferenkeh-Koroma, Ada, MaConnell, Helena, Ahwiren, Nyarko, Porter, Stephen, and Allcoa, Paul
Subjects: medicine.medical_specialty, business.industry, Immunology, Hydroxychloroquine, Placebo, Article, Rheumatology, B700, Clinical trial, B900, Internal medicine, Cohort, Immunology and Allergy, Medicine, Observational study, Rituximab, business, Depression (differential diagnoses), medicine.drug
Abstract: Summary Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjogren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjogren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjogren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjogren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology. Video Abstract Download : Download video (77MB) Symptom-based stratification of patients with Sjogren's syndrome
Published: 2019

22. A phase II randomised, double-blind, placebo-controlled, proof of concept study of oral seletalisib in patients with primary Sjögren’s syndrome (PSS)

Author: Juárez, Maria, Diaz, Nieves, Johnston, Geoffrey I, Nayar, Saba, Payne, Andrew, Helmer, Eric, Cain, Dionne, Williams, Paulette, Ng, Wan Fai, Fisher, Benjamin, Gottenberg, Jacques-Eric, Guggino, Giuliana, Mariette, Xavier, Kvarnström, Marika, Devauchelle-Pensec, Valérie, Rosas, Jose, Sanchez-Burson, Juan, Giacomelli, Roberto, Barone, Francesca, Bowman, Simon J, UCB Pharma Slough, University of Birmingham [Birmingham], UCB Pharma Raleigh, University of Newcastle, Newcastle upon Tyne, UK, University Hospital of Strasbourg, University of Palermo, Italy, Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Unit of Experimental Rheumatology, Stockhom (Department of Medicine), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital Marina Baixa, Villajoyosa, Infantaluisa Hospital, Sevilla, University of L'Aquila [Italy] (UNIVAQ), University Hospital Birmingham, UCB Pharma [Slough], UCB Pharma [Brussels], Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
Subjects: [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

23. Towards the lowest efficacious dose (toledo): results of a multicenter non-inferiority randomized open-label controlled trial assessing tocilizumab or abatacept injection spacing in rheumatoid arthritis patients in remission

Author: Joanna, KEDRA, Dieudé, Philippe, Marotte, Hubert, Lafourcade, Alexandre, Ducourau, Emilie, Schaeverbeke, Thierry, Perdriger, Aleth, Soubrier, Martin, Morel, Jacques, Constantin, Arnaud, Dernis, Emmanuelle, Royant, Valérie, Salmon, Jean-Hugues, Pham, Thao, Gottenberg, Jacques-Eric, Pertuiset, Edouard, Dougados, Maxime, Devauchelle-Pensec, Valérie, Gaudin, Philippe, Cormier, Gregoire, Goupille, Philippe, Mariette, Xavier, Berenbaum, Francis, Alcaix, Didier, Rouidi, Sid Ahmed, Berthelot, Jean-Marie, Monnier, Agnès, Piroth, Christine, Liote, Frederic, Goeb, Vincent, Gaujoux-Viala, Cécile, Valckenaere, Isabelle Chary, Hajage, David, Tubach, Florence, Fautrel, Bruno, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRI-IMIDIATE Clinical Research Network, Service de Rhumatologie [Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Hôpital Louis Pasteur [Chartres], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Hopital Réné Dubos, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Victor Jousselin de Dreux, Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Rhumatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière-Fernand-Widal [APHP], Service de Rhumatologie - AMIENS (AMIENS - Rhumato), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), DESSAIVRE, Louise, Michel, Geneviève, Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Department of Internal Medicine/Division of Rheumatology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, CHU Bordeaux [Bordeaux], Service de rhumatologie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, School of Informatics [Edimbourg], University of Edinburgh, Service de rhumatologie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Groupe de Recherche et d’Étude du Processus Inflammatoire (GREPI), Université Joseph Fourier - Grenoble 1 (UJF)-EFS, Centre Hospitalier Départemental Vendée, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Département d'épidémiologie, biostatistique et recherche clinique, Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-AP-HP, CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Service de Rhumatologie - CH Le Mans, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Groupe de Recherche et d'Etudes du Processus Inflammatoire (GREPI), Université Joseph Fourier - Grenoble 1 (UJF), Service de rhumatologie [Tours], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] (DHU i2B ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Hôpital Lariboisière, Service de rhumatologie [Rouen], AP-HP Hôpital universitaire Robert-Debré [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Tours (UT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Rhumatologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris]
Subjects: [SDV] Life Sciences [q-bio], [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: Annual European Congress of Rheumatology (EULAR), Madrid, SPAIN, JUN 12-15, 2019; International audience
Published: 2019

24. 2019 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF SJOGREN'S SYNDROME WITH TOPICAL AND SYSTEMIC THERAPIES

Author: Ramos-Casals, Manuel Brito-Zeron, Pilar Bombardieri, Stefano and Bootsma, Hendrika De Vita, Salvatore Doerner, Thomas Fisher, Benjamin A. Gottenberg, Jacques-Eric Hernandez-Molina, Gabriela and Kocher, Agnes Kostov, Belchin Kruize, Aike A. Mandl, Thomas Ng, Wan-Fai Retamozo, Soledad Seror, Raphaele and Shoenfeld, Yehuda Siso-Almirall, Antoni Tzioufas, Athanasios G. and Vitali, Claudio Bowman, Simon Mariette, Xavier and EULAR-Sjogren Syndrome Task Force
Published: 2019

25. Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors.: Prospective cohort study

Author: Gottenberg, Jacques, Morel, Jacques, Perrodeau, Elodie, Bardin, Thomas, Combe, Bernard, Dougados, Maxime, Flipo, René-Marc, Saraux, Alain, Schaeverbeke, Thierry, Sibilia, Jean, Soubrier, Martin, Vittecoq, Olivier, Baron, Gabriel, Constantin, Arnaud, Ravaud, Philippe, Mariette, Xavier, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lapeyronie [Montpellier] (CHU), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Bordeaux [Bordeaux], CHU Clermont-Ferrand, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), French Society of Rheumatology and the investigators participating in AIR, ORA, and REGATE registries, and Michel, Geneviève
Subjects: musculoskeletal diseases, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract: International audience; OBJECTIVE: To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) α inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis.DESIGN: Population based prospective study.SETTING: 53 university and 54 non-university clinical centres in France.PARTICIPANTS: 3162 adults (>18 years) with rheumatoid arthritis according to 1987 American College of Rheumatology criteria, enrolled in one of the three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months.INTERVENTION: Initiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis.MAIN OUTCOME MEASURE: The primary outcome was drug retention without failure at 24 months. Failure was defined as all cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease modifying antirheumatic drugs; or increase in corticosteroid dose >10 mg/d compared with baseline at two successive visits. Because of non-proportional hazards, treatment effects are presented as life expectancy difference without failure (LEDwf), which measures the difference between average duration of survival without failure.RESULTS: Average durations of survival without failure were 19.8 months for rituximab, 15.6 months for abatacept, and 19.1 months for tocilizumab. Average durations were greater with rituximab (LEDwf 4.1, 95% confidence interval 3.1 to 5.2) and tocilizumab (3.5, 2.1 to 5.0) than with abatacept, and uncertainty about tocilizumab compared with rituximab was substantial (-0.7, -1.9 to 0.5). No evidence was found of difference between treatments for mean duration of survival without death, presence of cancer or serious infections, or major adverse cardiovascular events.CONCLUSION: Among adults with refractory rheumatoid arthritis followed-up in routine practice, rituximab and tocilizumab were associated with greater improvements in outcomes at two years compared with abatacept.
Published: 2019

26. Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors

Author: Deodhar, Atul, Poddubnyy, Denis, Pacheco‐Tena, Cesar, Salvarani, Carlo, Lespessailles, Eric, Rahman, Proton, Järvinen, Pentti, Sanchez‐Burson, Juan, Gaffney, Karl, Lee, Eun Bong, Krishnan, Eswar, Santisteban, Silvia, Li, Xiaoqi, Zhao, Fangyi, Carlier, Hilde, Reveille, John, Antolini, Christopher, Azevedo, Valderilio, Barkham, Magnus, Rodriguez, Aaron Alejandro Barrera, Berman, Alberto, Blicharski, Tomasz, Brzezicki, Jan, Burmester, Gerd, Carrio, Judith, Collantes, Eduardo, Combe, Bernard, Cons‐Molina, Fidencio, Cortes‐Maisonet, Gregorio, Dudek, Anna, Barragan, Sergio Duran, Elkayam, Ori, Flint, Kathleen, Galeazzi, Mauro, Gaylis, Norman, Goddard, David, Fernandez, Carlos Gonzalez, Goupille, Philippe, Masmitja, Jordi Gratacos, Greenwald, Maria, Gremese, Elisa, Hong, Seung Jae, Howell, Mary, Hrycaj, Pawel, Ince, Akgun, Ju, Ji Hyeon, Kaine, Jeffrey, Kang, Seong Wook, Keiserman, Mauro, Kim, Tae‐Hwan, Kivitz, Alan, Klein, Steven, Kremer, Joel, Lee, Sang Heon, Lee, Chang Keun, Lee, Sang‐Hoon, Lidman, Roger, Loveless, James, Lucero, Eleonora, Cocco, Jose Maldonado, Marcolino, Flora, Mariette, Xavier, Mehta, Daksha, Morin, Frederic, Moscovici, Yolanda, Mueller, Eric, Mysler, Eduardo, Blasco, Francisco Navarro, Nguyen, Minh, Pantojas, Carlos, Park, Min‐Chan, Jesus, Amarilis Perez‐De, Peters, Eric, Plebanski, Rafal, Querubin, Roel, Remus, Cesar Ramos, Reitblat, Tatiana, Rivera, Tania, Rodriguez, Juan Cruz Rizo, Sayers, Michael, Scotton, Antonio, Scoville, Craig, Shaw, David, Shin, Kichul, Singhal, Atul, Skinner, Cassandra, Soto‐Raices, Oscar, Soubrier, Martin, Szymanska, Malgorzata, Thai, Christine, Sande, Marleen, Wells, Alvin, Wojciechowski, Rafal, Xavier, Ricardo, Ximenes, Antonio, Zisman, Devy, Imagerie Multimodale Multiéchelle et Modélisation du Tissu Osseux et articulaire (I3MTO), Université d'Orléans (UO), Oregon Health and Science University [Portland] (OHSU), Universidad Autónoma de Chihuahua (UACH), Università degli Studi di Modena e Reggio Emilia, Memorial University of Newfoundland [St. John's], Seoul National University [Seoul] (SNU), Eli Lilly and Company [Indianapolis], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Adult, Male, Settore MED/16 - REUMATOLOGIA, Immunology, ankylosing spondylitis, axial spondyloarthritis, ixekizumab, radiographic, Antibodies, Monoclonal, Humanized, Rheumatology, Double-Blind Method, Spondylarthritis, Spondyloarthritis, Immunology and Allergy, Humans, ComputingMilieux_MISCELLANEOUS, Axis, Cervical Vertebra, Middle Aged, Spine, Radiography, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Quality of Life, Female, Tumor Necrosis Factor Inhibitors, Original Article, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; OBJECTIVE:To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi).METHODS:In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed.RESULTS:A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging-evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group).CONCLUSION:Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.
Published: 2019

27. Phenotype of biopsy-proven patients with primary Sjögren syndrome lacking ro autoantibodies: high frequency of dryness symptoms with low systemic activity (big data Sjögren projct)

Author: Retamozo, Soledad, Acar-Denizli, Nihan, Ng, Wan Fai, Horvath, Ildiko Fanny, Rasmussen, Astrid, Seror, Raphaele, Xiaomei, LI, Baldini, Chiara, Gottenberg, Jacques-Eric, Sandhya, Pulukool, Quartuccio, Luca, Priori, Roberta, Hernandez-Molina, Gabriela, Armagan, Berkan, Kruize, Aike A, Kwok, Seung-Ki, Kvarnström, Marika, Praprotnik, Sonja, Sène, Damien, Gerli, Roberto, Solans-Laqué, Roser, Rischmueller, Maureen, Mandl, Thomas, Suzuki, Yasunori, Isenberg, David, Valim, Valeria, Sebastian, Agata, Nordmark, Gunnel, Bootsma, Hendrika, Nakamura, Hideki, Giacomelli, Roberto, Devauchelle-Pensec, Valérie, Hofauer, Benedikt, Bombardieri, Michele, Trevisani, Virginia Fernandes Moça, Hammenfors, Daniel, Pasoto, Sandra, Gheita, Tamer A, Atzeni, Fabiola, Morel, Jacques, Vollenveider, Cristina, Consani-Fernández, Sandra, Mariette, Xavier, Ramos-Casals, Manuel, Brito-Zerón, Pilar, Michel, Geneviève, INICSA, UNC, CONICED, Cordoba, Mimar Sinan Üniversitesi, University of Newcastle, Newcastle upon Tyne, UK, University of Debrecen Egyetem [Debrecen], Oklahoma Medical Research Foundation (OMRF), INSERM UMR972, SFR André Lwoff, Université Paris Sud, APHP Paul Brousse, Anhui Provincial Hosp, University of Pisa - Università di Pisa, Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Christian Medical College & Hospital, Rheumatology Clinic, Academic Hospital S.M. Della Misericordia, Udine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Hacettepe University = Hacettepe Üniversitesi, University Medical Center [Utrecht], Catholic University of Korea, Unit of Experimental Rheumatology, Stockhom (Department of Medicine), Department of Rheumatology (Dep Rheumato - Ljubljana - SLOVENIE), University Medical Centre Slovenia, Université Paris Diderot - Paris 7 (UPD7), University and Azienda Ospedaliera of Perugia, Vall d'Hebron University Hospital [Barcelona], The University of Western Australia (UWA), Malmö University Hospital, Lund University, Kanazawa University (KU), University College of London [London] (UCL), Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, University of Wrocław [Poland] (UWr), Uppsala Universitet [Uppsala], University Medical Center Groningen [Groningen] (UMCG), Nagasaki University, University of L'Aquila [Italy] (UNIVAQ), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Centre for Experimental Medicine and Rheumatology, London, Queen Mary University of London (QMUL), Federal University of Sao Paulo (Unifesp), Haukeland University Hospital, University of Bergen (UiB), Hospital das Clinicas, Cairo University, Messina and Milan Univ, Milan, University Hospital of Montpellier, German Hospital, Buenos Aires, Hospital Maciel, Université Paris-Sud - Paris 11 (UP11), Hospital Clinic (IDIBAPS), H. CIMA-Sanitas, Barcelona, Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

28. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

Author: Sieberts, Solveig K., Zhu, Fan, García-García, Javier, Stahl, Eli, Pratap, Abhishek, Pandey, Gaurav, Pappas, Dimitrios, Aguilar, Daniel, Anton, Bernat, Bonet, Jaume, Eksi, Ridvan, Fornés, Oriol, Guney, Emre, Li, Hongdong, Marín, Manuel Alejandro, Panwar, Bharat, Planas-Iglesias, Joan, Poglayen, Daniel, Cui, Jing, Falcao, Andre O., Suver, Christine, Hoff, Bruce, Balagurusamy, Venkat S. K., Dillenberger, Donna, Neto, Elias Chaibub, Norman, Thea, Aittokallio, Tero, Ammad-ud-din, Muhammad, Azencott, Chloe-Agathe, Bellón, Víctor, Boeva, Valentina, Bunte, Kerstin, Chheda, Himanshu, Cheng, Lu, Corander, Jukka, Dumontier, Michel, Goldenberg, Anna, Gopalacharyulu, Peddinti, Hajiloo, Mohsen, Hidru, Daniel, Jaiswal, Alok, Kaski, Samuel, Khalfaoui, Beyrem, Khan, Suleiman Ali, Kramer, Eric R., Marttinen, Pekka, Mezlini, Aziz M., Molparia, Bhuvan, Pirinen, Matti, Saarela, Janna, Samwald, Matthias, Stoven, Véronique, Tang, Hao, Tang, Jing, Torkamani, Ali, Vert, Jean-Phillipe, Wang, Bo, Wang, Tao, Wennerberg, Krister, Wineinger, Nathan E., Xiao, Guanghua, Xie, Yang, Yeung, Rae, Zhan, Xiaowei, Zhao, Cheng, Calaza, Manuel, Elmarakeby, Haitham, Heath, Lenwood S., Long, Quan, Moore, Jonathan D., Opiyo, Stephen Obol, Savage, Richard S., Zhu, Jun, Greenberg, Jeff, Kremer, Joel, Michaud, Kaleb, Barton, Anne, Coenen, Marieke, Mariette, Xavier, Miceli, Corinne, Shadick, Nancy, Weinblatt, Michael, de Vries, Niek, Tak, Paul P., Gerlag, Danielle, Huizinga, Tom W. J., Kurreeman, Fina, Allaart, Cornelia F., Louis Bridges Jr., S., Criswell, Lindsey, Moreland, Larry, Klareskog, Lars, Saevarsdottir, Saedis, Padyukov, Leonid, Gregersen, Peter K., Friend, Stephen, Plenge, Robert, Stolovitzky, Gustavo, Oliva, Baldo, Guan, Yuanfang, Mangravite, Lara M., Bridges, S. Louis, Intelligent Systems, Institute for Molecular Medicine Finland, Department of Mathematics and Statistics, Helsinki Institute for Information Technology, Jukka Corander / Principal Investigator, Department of Computer Science, Janna Saarela / Principal Investigator, Krister Wennerberg / Principal Investigator, Biostatistics Helsinki, Statistical and population genetics, AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology, Zhejiang University, Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), DYNBIO LEGOS, Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Institut d'Ecologia Aquàtica, Universitat de Girona (UdG), Department of Medical Genetics, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), China Agricultural University (CAU), Computational Intelligence Research Group (CA3), Centre of Technology and Systems (CTS), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Bioinformatique (CBIO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Hefei University of Technology (HFUT), Stanford Center for BioMedical Informatics Research (BMIR), Stanford University, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Technical Research Centre of Finland, VTT Technical Research Centre of Finland (VTT), U.S. Food and Drug Administration (FDA), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Profium Oy [Helsinki], Chinese Academy of Agricultural Sciences (CAAS), Business School [Hohai University], Hohai University, Institute of Industrial Economics [Hohai University], State Key Laboratory of Medical Genetics of China, Hunan Medical College, State Key Laboratory of Advanced Special Steel, Shanghai University, Quantitative Biomedical Research Center (QBRC), University of Texas Southwestern Medical Center [Dallas], Harold C. Simmons Comprehensive Cancer Center [Dallas, TX, États-Unis], Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), China National Research Center of Intelligent Equipment for Agriculture [Beijing] (NRCIEA), Centro Nacional de Análisi Genómico (CNAG), Centro Nacional de Análisis Genómico, Gregor Mendel Institute of Molecular Plant Biology (GMI), Austrian Academy of Sciences (OeAW), Department of Mechanical and Aerospace Engineering [Univ California Davis] (MAE - UC Davis), University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Tongji University, Laboratory for Measles and Rubella, Laboratoire National de Santé [Luxembourg] (LNS), Department of Human Genetics, Radboud University Medical Center [Nijmegen], INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), School of biosciences and biotechnology, University of Camerino, Università degli Studi di Camerino = University of Camerino (UNICAM), Division of Rheumatology, Immunology and Allergy and Partners Asthma Center, Brigham and Women's Hospital [Boston], Department of Health Education and Promotion, Maastricht University [Maastricht], University of Amsterdam [Amsterdam] (UvA), Department of rheumatology, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Rheumatology Unit, Department of Medicine, University of California [San Francisco] (UC San Francisco), University of California (UC), Rheumatology Unit, Karolinska Institutet [Stockholm], Merck & Co. Inc, Structural Bioinformatics Group (GRIB), Barcelona Research Park of Biomedicine (PRBB), Universitat Pompeu Fabra [Barcelona] (UPF), Capital Normal University [Beijing], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), MINES ParisTech - École nationale supérieure des mines de Paris, California Institute of Technology (CALTECH)-NASA, Department of Mechanical and Aerospace Engineering [Davis], University of California-University of California, Università degli Studi di Camerino (UNICAM), University of California [San Francisco] (UCSF), University of California, Sage Bionetworks, University of Michigan, Ann Arbor, Pompeu Fabra University, Icahn School of Medicine at Mount Sinai, Corrona LLC, Northeastern University, Harvard University, University of Lisbon, IBM, INSERM U900, University of Helsinki, University of Toronto, Scripps Research Institute, Medical University of Vienna, University of Texas at Dallas, New York University, Albany Medical College, Arthritis Research Center Foundation, Radboud University Nijmegen, INSERM U1184, University of Amsterdam, Glaxo Smith Kline, Leiden University, University of Alabama at Birmingham, University of California San Francisco, University of Pittsburgh, Karolinska Institutet, North Shore-Long Island Jewish Health System, Merck, Aalto-yliopisto, and Aalto University
Subjects: Male, 0301 basic medicine, General Physics and Astronomy, Arthritis, Genome-wide association study, Bioinformatics, DISEASE, Arthritis, Rheumatoid, Cohort Studies, Missing heritability problem, MISSING HERITABILITY, Medicine, Certolizumab pegol, RISK, Multidisciplinary, Antibodies, Monoclonal, Middle Aged, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, STACKED GENERALIZATION, Treatment Outcome, Antirheumatic Agents, Crowdsourcing, Biomarker (medicine), Female, Erratum, medicine.drug, Adult, Science, Context (language use), Antibodies, Monoclonal, Humanized, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, INFLIXIMAB, Journal Article, Humans, SNP, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, Aged, ta113, Tumor Necrosis Factor-alpha, business.industry, NETWORK INFERENCE, COMPLEX TRAITS, Artritis reumatoide -- Tractament, CLINICAL-RESPONSE, General Chemistry, 113 Computer and information sciences, medicine.disease, Infliximab, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, Certolizumab Pegol, business, RC
Abstract: Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data., Rheumatoid arthritis patients respond differently to anti-TNF treatment. Using community-based challenge, the authors show that currently available data does not reveal meaningful genetic predictors of response to anti-TNF therapy, thus confirming clinical observations.
Published: 2016

29. How immunological profile drives clinical phenotype of primary Sjögren’s syndrome at diagnosis: analysis of 10.500 patients (Sjögren Big data project

Author: Retamozo, Soledad, Acar-Denizli, Nihan, Ng, Wan-Fai, Rasmussen, Astrid, Mandl, Thomas, Seror, Raphaele, Li, Xiaomei, Baldini, Chiara, Gottenberg, Jacques-Eric, Danda, Debashish, Quartuccio, Luca, Priori, Roberta, Hernandez-Molina, Gabriala, Armagan, Berkan, Kruize, Aike A, Kwok, Seung-Ki, Kvarnström, Marika, Praprotnik, Sonja, Sène, Damien, Bartoloni, Elena, Solans, Roser, Rischmueller, Maureen, Suzuki, Yasunori, Isenberg, David A, Valim, Valeria, Wiland, Piotr, Nordmark, Gunnel, Fraile, Guadalupe, Bootsma, Hendrika, Nakamura, Takashi, Giacomelli, Roberto, Devauchelle-Pensec, Valérie, Knopf, Andreas, Bombardieri, Michele, Trevisani, Virginia Fernandes, Hammenfors, Daniel S, Pasoto, Sandra G, Gheita, Tamer A, Atzeni, Fabiola, Morel, Jacques, Vollenveider, Cristina, Horvath, Ildiko-Fanny, Sivils, Kathy L, Olsson, Peter, De Vita, Salvatore, Sánchez-Guerrero, Jorge, Kilic, Levent, Wahren-Herlenius, Marie, Mariette, Xavier, Ramos-Casals, Manuel, Brito-Zerón, Pilar, INICSA, UNC, CONICED, Cordoba, Rheumatology Unit, Cordoba (Institute University of Biomedical Sciences University of Cordoba (IUCBC), Department of Statistics, Istanbul, Mimar Sinan Üniversitesi, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], Oklahoma Medical Research Foundation (OMRF), Department of Rheumatology, Skane University Hospital, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Departement of Rheumatology and Immunology, Hefei (Anhui Provincial Hospital), Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Immunology and Rheumatology, Vellore (Christian Medical College & Hospital), Rheumatology Clinic, Academic Hospital S.M. Della Misericordia, Udine, Department of Internal Medicine [Rome, Italy] (DMISM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Immunology and Rheumatology Department, Mexico City, Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Hacettepe University = Hacettepe Üniversitesi, University Medical Center [Utrecht], Seoul St Mary's Hospital, Seoul, Unit of Experimental Rheumatology, Stockhom (Department of Medicine), Department of Rheumatology (Dep Rheumato - Ljubljana - SLOVENIE), University Medical Centre Slovenia, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Department of Medicine [Perugia, Italy] (Rheumatology, Unit), Università degli Studi di Perugia (UNIPG), Vall d'Hebron University Hospital [Barcelona], The Queen Elizabeth Hospital, Adelaide, Human Information Processing Laboratory - Japanese Advances Institute of Science and Technology [Ishikawa] (HIP/JAIST), JAIST - Ishikawa - Japon, Centre for Rheumatology and Connective Tissue Diseases (University College London, Royal Free Hospital), Centre for Rheumatology - London, Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, Department of Rheumatology and Internal Medicine, Wroclaw, Department of Medical Sciences, Uppsala (Section of Rheumatology), Department of Internal Medicine, Madrid, Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), Department of Radiology and Cancer Biology, Nagasaki, University of L'Aquila [Italy] (UNIVAQ), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Otorhinolaryngology/Head and Neck Surgery, Munich, Centre for Experimental Medicine and Rheumatology, London, Federal University of São Paulo, Department of Clinical Science and Department of Rheumatology, Bergen, Rheumatology Division, Hospital das Clinicas, Sao Paulo (HCFMUSP), Rheumatology Department, Cairo, Istituto Ortopedico Galeazzi-IRCCS, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, German Hospital, Buenos Aires, Department of Immunology [Debrecen, Hungary], University of Debrecen [Hungary], Department of Rheumatology (Dep Rheumato - Malmo - SUEDE), Skåne University Hospital, Department of Medical Area, University Hospital Santa Maria della Misericordia, Udine, Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Department of Immunology [Mexico City], Natl Inst Pediat, Immunodeficiencies Res Unit, Mexico City, DF, Mexico, Rheumatology, Hacetttepe University Faculty of Medicine, Ankara, Department of Medicine Solna, CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, University of Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Systemic Autoimmune Disease Unit, Department of Internal Medicine, Vall d'Hebron University Hospital, Barcelona, Spain, Department of Medicine, Universitat Autonòma, Barcelona, CHU Cochin [AP-HP], Sapienza University [Rome], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, University Hospital 'Santa Maria della Misericordia', and Michel, Geneviève
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

30. Low Influenza, Pneumococcal and Diphtheria–Tetanus–Poliomyelitis Vaccine Coverage in Patients with Primary Sjögren’s Syndrome: A Cross-Sectional Study

Author: Mariette Xavier, Hind Letaief, Cédric Lukas, Guilpain Philippe, Morel Jacques, Combe Bernard, Service de Rhumatologie [CHU de Montpellier], CHU Montpellier, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, medicine.medical_specialty, genetic structures, Referral, Cross-sectional study, Influenza vaccine, Immunology, Population, coverage, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Drug Discovery, Medicine, Pharmacology (medical), education, 030203 arthritis & rheumatology, Pharmacology, education.field_of_study, business.industry, Odds ratio, vaccination, Confidence interval, 3. Good health, Vaccination, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030104 developmental biology, Infectious Diseases, Pneumococcal vaccine, Sjögren’s syndrome, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business
Abstract: Objective: To evaluate vaccination coverage and reasons for non-vaccination in patients with primary Sj&ouml, gren&rsquo, s syndrome (pSS). Method: A total of 111 patients fulfilling American&ndash, European Consensus Group criteria for pSS were interviewed by use of a standardized questionnaire between January 2016 and November 2017 in two French tertiary referral centers for auto-immune diseases. Results: Updated immunization coverage for influenza was 31.5% (n = 35), pneumococcus was 11.7% (n = 13), and diphtheria&ndash, tetanus&ndash, poliomyelitis (DTP) was 24.3% (n = 27). The main reasons for non-vaccination were fear of side effects from the influenza vaccine (40.3%) and a lack of proposal for the pneumococcal vaccine (72.3%). In vaccinated patients, vaccination was mainly proposed by general practitioners for the influenza vaccine (42.6%) and rheumatologists for the pneumococcal vaccine (41.2%). Probability of influenza vaccination was associated with age (odds ratio/year (OR) 1.04, 95% confidence interval (CI) 1.0&ndash, 1.1, p = 0.016), history of severe infection (OR 15.9, 95% CI 1.35&ndash, 186, p = 0.028), low EULAR Sj&ouml, s syndrome disease activity index (OR 0.85, 95% CI 0.75&ndash, 0.96, p = 0.013), and comorbidities (OR 3.52, 95% CI 1.22&ndash, 10.2, p = 0.02). Probability of vaccination against pneumococcus was associated with lung comorbidities (OR 3.83, 95% CI 1.11&ndash, 13.12, p = 0.033) and up-to-date influenza vaccination (OR 3.71, 95% CI 1.08&ndash, 12.8, p = 0.038). Conclusion: Influenza, pneumococcal, and DTP vaccine coverage was low in patients with pSS included in this study. These results underline the relevance of systematically screening vaccine status in pSS patients and educating patients and physicians on the need for vaccination to improve vaccine coverage in this population.
Published: 2019

31. Low Percentage of Signal Regulatory Protein α/β

Author: Magill, Laura, Adriani, Marsilio, Berthou, Véronique, Chen, Keguan, Gleizes, Aude, Hacein-Bey-Abina, Salima, Hincelin-Mery, Agnes, Mariette, Xavier, Pallardy, Marc, Spindeldreher, Sebastian, Szely, Natacha, Isenberg, David A., Manson, Jessica J., Jury, Elizabeth C., and Mauri, Claudia
Subjects: rheumatoid arthritis, Adult, Male, Immunology, Receptors, Cell Surface, immunogenicity, Arthritis, Rheumatoid, Drug Hypersensitivity, memory B cells, Humans, Lymphocyte Count, Prospective Studies, Receptors, Immunologic, Neural Cell Adhesion Molecules, Original Research, Aged, B cells, B-Lymphocytes, Tumor Necrosis Factor-alpha, SIRP, Adalimumab, anti-TNF, Middle Aged, Prognosis, Antigens, Differentiation, anti-drug antibodies, Cross-Sectional Studies, Antirheumatic Agents, Female, Immunologic Memory, Biomarkers
Abstract: An important goal for personalized treatment is predicting response to a particular therapeutic. A drawback of biological treatment is immunogenicity and the development of antibodies directed against the drug [anti-drug antibodies (ADA)], which are associated with a poorer clinical outcome. Here we set out to identify a predictive biomarker that discriminates rheumatoid arthritis (RA) patients who are more likely to develop ADA in response to adalimumab, a human monoclonal antibody against tumor necrosis factor (TNF)α. By taking advantage of an immune-phenotyping platform, LEGENDScreen™, we measured the expression of 332 cell surface markers on B and T cells in a cross-sectional adalimumab-treated RA patient cohort with a defined ADA response. The analysis revealed seven differentially expressed markers (DEMs) between the ADA+ and ADA− patients. Validation of the DEMs in an independent prospective European cohort of adalimumab treated RA patients, revealed a significant and consistent reduced frequency of signal regulatory protein (SIRP)α/β-expressing memory B cells in ADA+ vs. ADA− RA patients. We also assessed the predictive value of SIRPα/β expression in a longitudinal RA cohort prior to the initiation of adalimumab treatment. We show that a frequency of < 9.4% of SIRPα/β-expressing memory B cells predicts patients that will develop ADA, and consequentially fail to respond to treatment, with a receiver operating characteristic (ROC) area under the curve (AUC) score of 0.92. Thus, measuring the frequency of SIRPα/β-expressing memory B cells in patients prior to adalimumab treatment may be clinically useful to identify a subgroup of active RA subjects who are going to develop an ADA response and not gain substantial clinical benefit from this treatment.
Published: 2018

32. How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis: analysis of 10.500 patients (Sjögren big data project)

Author: Retamozo, Soledad, Acar-Denizli, Nihan, Ng, Wan-Fai, Zeher, Margit, Rasmussen, Astrid, Mandl, Thomas, Seror, Raphaele, Li, Xiaomei, Baldini, Chiara, Gottenberg, Jacques-Eric, Danda, Debashish, Quartuccio, Luca, Priori, Roberta, Hernandez-Molina, Gabriela, Armagan, Berkan, Kruize, Aike A., Kwok, Seung-Ki, Kvarnstrom, Marika, Praprotnik, Sonja, Sene, Damien, Bartoloni, Elena, Solans, Roser, Rischmueller, Maureen, Suzuki, Yasunori, Isenberg, David A., Valim, Valeria, Wiland, Piotr, Nordmark, Gunnel, Fraile, Guadalupe, Bootsma, Hendrika, Nakamura, Takashi, Giacomelli, Roberto, Devauchelle-Pensec, Valerie, Knopf, Andreas, Bombardieri, Michele, Trevisani, Virginia Fernandes, Hammenfors, Daniel S., Pasoto, Sandra G., Gheita, Tamer A., Atzeni, Fabiola, Morel, Jacques, Vollenveider, Cristina, Horvath, Ildiko-Fanny, Sivils, Kathy L., Olsson, Peter, Vita, Salvatore, Sanchez-Guerrero, Jorge, Kilic, Levent, Wahren-Herlenius, Marie, Mariette, Xavier, Manuel Ramos-Casals, Brito-Zeron, Pilar, Michel, Geneviève, H. CIMA-Sanitas, Barcelona, Departement of Statistics, Istanbul, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], Department of Immunology [Debrecen, Hungary], University of Debrecen [Hungary], Oklahoma Medical Research Foundation (OMRF), Department of Rheumatology (Dep Rheumato - Malmo - SUEDE), Skåne University Hospital, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Departement of Rheumatology and Immunology, Hefei (Anhui Provincial Hospital), Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Department of Clinical Immunology and Rheumatology, Vellore (Christian Medical College & Hospital), Rheumatology Clinic, Academic Hospital S.M. Della Misericordia, Udine, Department of Internal Medicine and Medical Specialties, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Immunology [Mexico City], Natl Inst Pediat, Immunodeficiencies Res Unit, Mexico City, DF, Mexico, Department of Internal Medicine, Ankara (Hacettepe University), University Medical Center [Utrecht], Seoul St Mary's Hospital, Seoul, Karolinska Institutet, Department of Rheumatology, Karolinska University Hospital [Stockholm], Department of Rheumatology (Dep Rheumato - Ljubljana - SLOVENIE), University Medical Centre Slovenia, Département de Médecine interne [Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Department of Medicine [Perugia, Italy] (Rheumatology, Unit), Università degli Studi di Perugia (UNIPG), Department of Internal Medicine, Barcelona, The University of Western Australia (UWA), Division of Rheumatology Kanazawa University Graduate School of Medicine, Kanazawa, Centre for Rheumatology - London, Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, Department of Rheumatology and Internal Medicine, Wroclaw, Department of Medical Sciences, Uppsala (Section of Rheumatology), Department of Internal Medicine, Madrid, Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), Department of Radiology and Cancer Biology, Nagasaki, Clinical Unit of Rheumatology, L'Aquila, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Otorhinolaryngology/Head and Neck Surgery, Munich, Centre for Experimental Medicine and Rheumatology, London, University of São Paulo (USP), Department of Clinical Science and Department of Rheumatology, Bergen, Rheumatology Division, Hospital das Clinicas, Sao Paulo (HCFMUSP), Universidad Nacional de Córdoba [Argentina], Rheumatology Department, Cairo, Istituto Ortopedico Galeazzi-IRCCS, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, German Hospital, Buenos Aires, Department of Rheumatology, Skane University Hospital, Immunology and Rheumatology Department, Mexico City, Department of Internal Medicine, Ankara, Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden, and CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

33. Low Percentage of Signal Regulatory Protein alpha/beta(+) Memory B Cells in Blood Predicts Development of Anti-drug Antibodies (ADA) in Adalimumab-Treated Rheumatoid Arthritis Patients

Author: Magill, Laura, Adriani, Marsilio, Berthou, Veronique, Chen, Keguan, Gleizes, Aude, Hacein-Bey-Abina, Salima, Hincelin-Mery, Agnes, Mariette, Xavier, Pallardy, Marc, Spindeldreher, Sebastian, Szely, Natacha, Isenberg, David A., Manson, Jessica J., Jury, Elizabeth C., Mauri, Claudia, ORANGE, Colette, University College of London [London] (UCL), Sanofi Aventis R&D [Chilly-Mazarin], GlaxoSmithKline, Glaxo Smith Kline, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Novartis Pharma AG, University College London Hospitals (UCLH), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, LONG-TERM TREATMENT, TREATMENT FAILURE, INFLIXIMAB, [SDV.IMM]Life Sciences [q-bio]/Immunology, ASSOCIATION, IMMUNOGENICITY, EFFICACY, TOCILIZUMAB, TREATMENT RESPONSE, TNF TREATMENT, DISEASE
Abstract: International audience; An important goal for personalized treatment is predicting response to a particular therapeutic. A drawback of biological treatment is immunogenicity and the development of antibodies directed against the drug [anti-drug antibodies (ADA)], which are associated with a poorer clinical outcome. Here we set out to identify a predictive biomarker that discriminates rheumatoid arthritis (RA) patients who are more likely to develop ADA in response to adalimumab, a human monoclonal antibody against tumor necrosis factor (TNF)alpha. By taking advantage of an immune-phenotyping platform, LEGENDScreen (TM), we measured the expression of 332 cell surface markers on B and T cells in a cross-sectional adalimumab-treated RA patient cohort with a defined ADA response. The analysis revealed seven differentially expressed markers (DEMs) between the ADA(+) and ADA(-) patients. Validation of the DEMs in an independent prospective European cohort of adalimumab treated RA patients, revealed a significant and consistent reduced frequency of signal regulatory protein (SIRP)alpha/beta-expressing memory B cells in ADA(+ )vs. ADA(-) RA patients. We also assessed the predictive value of SIRP alpha/beta-expression in a longitudinal RA cohort prior to the initiation of adalimumab treatment. We show that a frequency of
Published: 2018

34. Association of the Presence of Anti-Carbamylated Protein Antibodies in Early Arthritis With a Poorer Clinical and Radiologic Outcome

Author: Truchetet, Marie-Elise, Dublanc, Stéphanie, Barnetche, Thomas, Vittecoq, Olivier, Mariette, Xavier, Richez, Christophe, Blanco, Patrick, Mahler, Michael, Contin-Bordes, Cécile, Schaeverbeke, Thierry, Saraux, Alain, Immunology and Allergy, University Hospital and School of Medicine, Université de Bordeaux (UB), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), INOVA Diagnostics, San Diego, Service de rhumatologie, CHU Bordeaux [Bordeaux], and Calvez, Ghislaine
Subjects: [SDV] Life Sciences [q-bio], [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2017

35. Modification of the classification criteria for primary Sjögren syndrome: an international vignette survey

Author: Jousse-Joulin, Sandrine, Gatineau, Florence, Baldini, Chiara, Baer, Alan N., Barone, Francesca, Bootsma, Hendrika, Bowman, Simon, Zeron, Pilar Brito, Cornec, Divi, Doerner, Thomas, De Vita, Salvatore, Fisher, Benjamin, Hammenfors, Daniel S., Jonsson, Malin V., Mariette, Xavier, Milic, Vera, Nakamura, Hideki, Ng, Wan-Fai, Nowak, Emmanuel, Ralos-Casals, Manuel, Rasmussen, Astrid, Seror, Raphaele, Shiboski, Caroline, Nakamura, Takashi, Vissink, Arjan, Saraux, Alain, Devauchelle-Pensec, Valerie, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Johns Hopkins University School of Medicine [Baltimore], University of Birmingham [Birmingham], University of Groningen [Groningen], Department of Rheumatology, University Hospital Birmingham, Department of Internal Medicine, Barcelona, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rheumatology Clinic, Academic Hospital S.M. Della Misericordia, Udine, Univeristy of Birmingham, Broegelmann Research Laboratory, Department of Clinical Science, Section for Oral and Maxillofacial Radiology, Bergen, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), University of Belgrade [Belgrade], Department of Immunology and Rheumatology, Nagasaki, Japan, University of Newcastle, Newcastle upon Tyne, UK, University of Barcelona, Oklahoma Medical Research Foundation, Medical Research Foundation, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Departments of Orofacial Sciences and Pediatrics, University of California, Department of Radiology and Cancer Biology, Nagasaki, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Michel, Geneviève, Translational Immunology Groningen (TRIGR), and Personalized Healthcare Technology (PHT)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

36. Is there a seasonal effect on fatigue, pain and dryness in primary Sjögren's syndrome? Data from the prospective assess cohort and from 3 randomized controlled trials

Author: Duret, Pierre-Marie, Meyer, Nicolas, Saraux, Alain, Devauchelle-Pensec, Valérie, Sibilia, Jean, Seror, Raphaèle, Le Guern, Veronique, Larroche, Claire, Perdriger, Aleth, Mariette, Xavier, Gottenberg, Jacques-Eric, Hôpital de Hautepierre [Strasbourg], CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Internal Medicine, Paris, Centre Hospitalier Universitaire [Rennes], Univ. Paris-Sud, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

37. Epidemiologic subsets drive a differentiated clinical and immunological presentation of primary Sjögren syndrome: analysis of 9302 patients from the big data International Sjögren Cohort

Author: Retamozo, Soledad, Brito-Zeron, Pilar, Zeher, Margit, Sivils Kathy, L, Seror, Raphaele, Mandl, Thomas, Li, Xiaomei, Baldini, Chiara, Gottenberg, Jacques-Eric, Danda, Debashish, Priori, Roberta, Quartuccio, Luca, Hernandez-Molina, Gabriela, Kruize Aike, A., Kwok, Seung-Ki, Wahren-Herlenius, Marie, Sene, Damien, Gerli, Roberto, Solans, Roser, Suzuki, yasunori, Isenberg David, A., Rischmueller, Maureen, Nordmark, Gunnel, Fraile, Guadalupe, Wiland, Piotr, Bootsma, Hendrika, Nakamura, Takashi, Valim, Valeria, Giacomelli, Roberto, Devauchelle-Pensec, Valérie, Hofauer, Benedikt, Bombardieri, Michèle, Fernandes Moça Trevisani, Virginia, Hammenfors, Daniel S., Carsons Steven, E., Pasoto, Gofinet, Morel, Jacques, Gheita, Tamer, Atzeni, Fabiola, Vollenweider, Cristina F., Kostov, Belchin, Mariette, Xavier, Ramos-Casals, Manuel, Rheumatology Unit, Cordoba (Institute University of Biomedical Sciences University of Cordoba (IUCBC), Autoimmune Diseases Unit, Barcelona (Department of Medicine), Department of Immunology [Debrecen, Hungary], University of Debrecen [Hungary], Oklahoma Medical Research Foundation, Medical Research Foundation, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Department of Rheumatology, Skane University Hospital, Department of Rheumatology and Immunology, Hefei, Anhui, Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Rheumatology [CHU Strasbourg], CHU Strasbourg, Clinical Immunology & Rheumatology, Vellore, UO Complessa Reumatologia, Rome, Rheumatology Clinic, Udine (DSMB), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], University Medical Center [Utrecht], Division of Rheumatology, Seoul (Department of Internal Medicine), Unit of Experimental Rheumatology, Stockhom (Department of Medicine), Département de Médecine interne [Lariboisière], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University and Azienda Ospedaliera of Perugia, Autoimmune Systemic Diseases Unit, Barcelona (Department of Internal Medicine), Division of Rheumatology Kanazawa University Graduate School of Medicine, Kanazawa, Centre for Rheumatology and Connective Tissue Diseases (University College London, Royal Free Hospital), Centre for Rheumatology - London, The Queen Elizabeth Hospital, Adelaide, Department of Medical Sciences, Uppsala (Section of Rheumatology), Autoimmune Diseases Department, Madrid, Wroclaw Medical University, University of Groningen [Groningen], Department of Radiology and Cancer Biology, Nagasaki, Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, University of L'Aquila [Italy] (UNIVAQ), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hals-Nasen-Ohrenklinik und Poliklinik, Munchen, The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London (QMUL), Université Fédérale de São Paulo (Unifesp), University of Bergen (UiB), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Department of Internal Medicine. Faculty of Medicine. University of São Paulo-RP, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Rheumatology Department, Cairo, Rheumatology Unit, Milano (ASST Fatebenefratelli-Sacco), Rheumatology, Buenos Aires, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Université Paris-Sud - Paris 11 (UP11), CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Michel, Geneviève, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

38. Off-label use of rituximab for systemic lupus erythematosus in Europe

Author: Ryden-Aulin, Monica, Boumpas, Dimitrios, Bultink, Irene, Rubio, Jose Luis Callejas, Caminal-Montero, Luis, Castro, Antoni, Colodro Ruiz, Agustin, Doria, Andrea, Domer, Thomas, Gonzalez-Echavarri, Cristina, Gremese, Elisa, Houssiau, Frederic A., Huizinga, Tom, Inana, Murat, Isenberg, David, Luliano, Annamaria, Jacobsen, Soren, Jimenez-Alonso, Juan, Kovacs, Laszlo, Mariette, Xavier, Mosca, Marta, Nived, Ola, Oristrell, Joaquim, Ramos-Casals, Manuel, Rascon, Javier, Ruiz-Irastorza, Guillermo, Saez-Comet, Luis, Salvador Cervello, Gonzalo, Cervello, Gonzalo Salvador, Sebastiani, Gian Domenico, Squatrito, Danilo, Szucs, Gabriella, Voskuyl, Alexandre, van Vollenhoven, Ronald, Rheumatology, AII - Inflammatory diseases, [Ryden-Aulin, Monica] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Clin Therapy Res, Stockholm, Sweden, [van Vollenhoven, Ronald] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Clin Therapy Res, Stockholm, Sweden, [Boumpas, Dimitrios] Natl & Kapodestrian Univ Athens, Attikon Univ Hosp, Joint Acad Rheumatol Program, Med Sch, Athens, Greece, [Boumpas, Dimitrios] Natl & Kapodestrian Univ Athens, Attikon Univ Hosp, Dept Med 4, Med Sch, Athens, Greece, [Bultink, Irene] Amsterdam Rheumatol & Immunol Ctr, Tepartment Rheumatol, Amsterdam, Netherlands, [Rubio, Jose Luis Callejas] Hosp San Cecilio, Unit Autoimmune Dis, Granada, Spain, [Caminal-Montero, Luis] Hosp Univ Cent Asturias, Internal Med Dept, Autoimmune System Dis Unit, Oviedo, Spain, [Castro, Antoni] Rovira & Virgili Univ URV, Univ Hosp Sant Joan Reus, lnternal Med Dept Univ, IISPV, Reus, Spain, [Colodro Ruiz, Agustin] Pasaje Nueva Victoria,2,2do C, Jaen, Spain, [Doria, Andrea] Univ Padua, Dept Med, Rheumatol Unit, Padua, Italy, [Domer, Thomas] Charite Univ Med Berlin, Dept Med Rheumatol & Clin Immunol, Berlin, Germany, [Gonzalez-Echavarri, Cristina] Univ Basque Country, Cruces Univ Hosp, BioCruces Hlth Res Inst, Autoimmune Dis Res Unit,Dept Internal Med, Baracaldo, Spain, [Ruiz-Irastorza, Guillermo] Univ Basque Country, Cruces Univ Hosp, BioCruces Hlth Res Inst, Autoimmune Dis Res Unit,Dept Internal Med, Baracaldo, Spain, [Gremese, Elisa] Univ Cattolica Sacro Cuore, Inst Rheumatol & Affine Sci IRSA, Rome, Italy, [Houssiau, Frederic A.] Catholic Univ Louvain, Pole Pathol Rhumatismales Inflammatoires & Syst, Clin Univ St Luc, Serv Rhumatol, Brussels, Belgium, [Huizinga, Tom] Leiden Univ, Med Ctr, Dept Rheumatol, C1-41, Leiden, Netherlands, [Inana, Murat] Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Rheumatol, Istanbul, Turkey, [Isenberg, David] UCL, Rayne Bldg, London, England, [Luliano, Annamaria] San Camillo Hosp, Rheumatol Unit, Rome, Italy, [Jacobsen, Soren] Univ Copenhagen, Rigshosp, Ctr Rheumatol & Spine Dis, Copenhagen Lupus & Vasculitis Clin, Copenhagen, Denmark, [Jimenez-Alonso, Juan] Univ Virgen Nieves Hosp, lnternal Dept, Granada, Spain, [Kovacs, Laszlo] Univ Szeged, Albert Szent Gyorgyi Hlth Ctr, Fac Med, Dept Rheumatol, Szeged, Hungary, [Mariette, Xavier] Univ Paris Sud, Hopitaux Univ Paris Sud, Rhumatol Responsable Unite Rech Clin, INSERM U1184, Paris, France, [Mosca, Marta] Rheumatol Unit, Pisa, Italy, [Nived, Ola] Skane Univ Hosp, Rheumatol Clin, Lund, Sweden, [Oristrell, Joaquim] Univ Autonoma Barcelona, Hosp Sabadell, Internal Med Dept, Catalunya, Spain, [Ramos-Casals, Manuel] CELLEX IDIBAPS, Josep Font Autoimmune Lab, ICMiD, Dept Autoimmune Dis, Barcelona, Spain, [Rascon, Javier] Carrer Sabateres, 9-1,Alare, Islas Baleares, Spain, [Saez-Comet, Luis] Hosp Univ Miguel Servet Zaragoza, Unidad Enfermedades Autoinmunes Sistem, Paseo Isabel Catolica, Zaragoza, Spain, [Salvador Cervello, Gonzalo] Hosp Univ & Politecn La Fe, Inmunopathol & Autoimmune Area, Dept Internal Med, Valencia, Spain, [Sebastiani, Gian Domenico] Osped San Camillo, UOC Reumatol, Circonvallaz Gianicolense 87, Rome, Italy, [Squatrito, Danilo] Univ Florence, Dept Sperimental & Clin Med, Florence, Italy, [Szucs, Gabriella] Univ Debrecen, Inst Med, Dept Rheumatol, Debrecen, Hungary, [Voskuyl, Alexandre] Vrije Univ Amsterdam, Med Ctr, Amsterdam Rheumatol & Immunol Ctr ARC, Amsterdam, Netherlands, [van Vollenhoven, Ronald] Karolinska Univ Hosp Stockholm, Rheumatol Clin, Stockholm, Sweden, [van Vollenhoven, Ronald] Amsterdam Rheumatol & Immunol Ctr ARC, AMC Mail F4-105, Amsterdam, Netherlands, MSD, Lilly Netherlands, Roche, UCB, Sanofi, and RvV
Subjects: medicine.medical_specialty, Disease duration, Immunology, Lupus nephritis, DMARDs (biologic), Klinikai orvostudományok, Off-label use, Systemic Lupus Erythematosus, Article, Disease activity, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, medicine, Lupus Nephritis, Medicine (all), In patient, 030212 general & internal medicine, skin and connective tissue diseases, 030203 arthritis & rheumatology, business.industry, Orvostudományok, General Medicine, medicine.disease, Disease control, 3. Good health, Rituximab, business, medicine.drug
Abstract: OBJECTIVES: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy.METHODS: Data on patients with SLE receiving RTX were taken from the International Registry for Biologics in SLE retrospective registry and complemented with data on patients with SLE treated with conventional therapy. For nationwide estimates of RTX use in patients with SLE, investigators were asked to provide data through case report forms (CRFs). Countries for which no data were submitted through CRFs, published literature and/or personal communication were used, and for European countries where no data were available, estimates were made on the assumption of similarities with neighbouring countries.RESULTS: The estimated off-label use of RTX in Europe was 0.5%-1.5% of all patients with SLE. In comparison with patients with SLE on conventional therapy, patients treated with RTX had longer disease duration, higher disease activity and were more often treated with immunosuppressives. The most frequent organ manifestations for which either RTX or conventional therapy was initiated were lupus nephritis followed by musculoskeletal and haematological. The reason for treatment was, besides disease control, corticosteroid-sparing for patients treated with conventional therapy.CONCLUSIONS: RTX use for SLE in Europe is restrictive and appears to be used as a last resort in patients for whom other reasonable options have been exhausted.
Published: 2016

39. Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors

Author: Hamze, Moustafa, Meunier, Sylvain, Karle, Anette, Gdoura, Abdelaziz, Goudet, Amélie, Szely, Natacha, Pallardy, Marc, Carbonnel, Franck, Spindeldreher, Sebastian, Mariette, Xavier, Miceli-Richard, Corinne, and Maillère, Bernard
Subjects: lcsh:Immunologic diseases. Allergy, rituximab, MHC-associated peptide proteomics, Immunology, antidrug antibody, CD4 T cell epitopes, therapeutic antibodies, immunogenicity, infliximab, lcsh:RC581-607, healthy donors, Original Research
Abstract: The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFα infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA)-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs) loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having developed ADAs against Rtx or Ifx and promoted the secretion of a diversity of cytokines. These data emphasize the predictive value of evaluating the T cell repertoire of healthy donors and the composition of peptides bound to HLA-DR of DCs to anticipate and prevent immunogenicity of therapeutic antibodies.
Published: 2017

40. Type I High-IFN Gene Signature in Associated with Higher Essdai at Enrollmment and Follow-up in the Prospective Multicenter Assess Cohort of 395 Patients

Author: Gottenberg, Jacques-Eric, Bost, Pierre-Etienne, Schwikowski, Benno, Seror, Raphaele, Devauchelle-Pensec, Valerie, Dieude, Philippe, Dubost, Jean-Jacques, Fauchais, Anne Laure, Goeb, Vincent, Hachulla, Eric, Hatron, Pierre Yves, Larroche, Claire, Le-Guern, Veronique, Morel, Jacques, Perdriger, Aleth, Dernis, Emmanuelle, Bouillon, Stephanie Rist, Saraux, Alain, Damien SENE, Sibilia, Jean, Vittecoq, Olivier, Nocturne, Gaetane, Tubiana, Sarah, Ravaud, Philippe, Mariette, Xavier, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], System Biologique, Paris, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Rhumatologie [CHU Gabriel-Montpied], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Rhumatologie - AMIENS (AMIENS - Rhumato), CHU Amiens-Picardie, Université de Lille, Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), CHU Pitié-Salpêtrière [AP-HP], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre, DESSAIVRE, Louise, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

41. Corticosteroid Sparing Effect of Non-TNF Targeted Biologics, Rituximab, Abatacept and Tocilizumab in Common Practice: Data from 3183 Patients Enrolled in the French Society of Rheumatology Registries

Author: Gottenberg, Jacques-Eric, Morel, Jacques, Constantin, Arnaud, Bardin, Thomas, Cantagrel, Alain, Combe, Bernard, Dougados, Maxime, Flipo, René-Marc, Saraux, Alain, Schaeverbeke, Thierry, Sibilia, Jean, Soubrier, Martin, Vittecoq, Olivier, Baron, Gabriel, Perrodeau, Elodie, Ravaud, Philippe, Mariette, Xavier, Michel, Geneviève, Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lapeyronie [Montpellier] (CHU), School of Informatics [Edimbourg], University of Edinburgh, Service de rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de rhumatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Rhumatologie (LILLE - Rhumatologie), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), CHU Clermont-Ferrand, CHU Rouen, Normandie Université (NU), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Orthopédique et traumatique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Lapeyronie [Montpellier] ( CHU ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Département de Rhumatologie ( LILLE - Rhumatologie ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Lymphocyte B et Auto-immunité ( LBAI ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Immunorhumathologie moléculaire, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: registries and rheumatoid arthritis (RA), [SDV.IMM] Life Sciences [q-bio]/Immunology, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS, corticosteroids
Abstract: International audience
Published: 2017

42. The role of rare protein-coding variants to anti-TNF treatment response in rheumatoid arthritis

Author: Cui, Jing, Diogo, Dorothee, Stahl, Eli A, Canhao, Helena, Mariette, Xavier, Greenberg, Jeffrey D, Okada, Yukinori, Pappas, Dimitrios A, Fulton, Robert S, Tak, Paul P, Nurmohamed, Michael T, Lee, Annette, Larson, David E, Kurreeman, Fina, Deluca, Tracie L, O'Laughlin, Michelle, Fronick, Catrina C, Fulton, Lucinda L, Mardis, Elaine R, van der Horst-Bruinsma, Irene E, Wolbink, Gert-Jan, Gregersen, Peter K, Kremer, Joel M, Crusius, J Bart A, de Vries, Niek, Huizinga, Tom W J, Fonseca, João Eurico, Miceli-Richard, Corinne, Karlson, Elizabeth W, Coenen, Marieke Jh, Barton, Anne, Plenge, Robert M, Raychaudhuri, Soumya, AII - Inflammatory diseases, Rheumatology, and ICaR - Circulation and metabolism
Abstract: Objective Many rheumatoid arthritis (RA) patients have their disease controlled with anti-tumor necrosis factor alpha (anti-TNF) biologic therapies. However, a significant number of RA patients fail to respond to anti-TNF therapy. Here, we hypothesized that rare and low-frequency variants might influence anti-TNF treatment response. Methods We sequenced the coding region of 750 genes in 1,094 RA patients of European ancestry treated with anti-TNF medications. After quality control, we included 690 genes in the analysis. We applied single variants association and gene-based association tests to identify variants associated with anti-TNF treatment response. We also performed gene set analyses of 27 TNF pathway genes, considering TNF's key mechanistic role. Results We identified 14,420 functional variants, of which 6,934 were predicted as non-synonymous where 2,136 were further predicted to be damaging. Despite being a well-powered study, no single variant or gene showed study-wide significant association with change in disease activity outcome or EULAR response outcome. Intriguingly, we observed 3 genes, out of 27 with nominal signals of association (P
Published: 2017

43. Outcome measures for primary Sjogren's syndrome

Author: Seror, Raphaèle, Theander, Elke, Bootsma, Hendrika, Bowman, Simon J, Tzioufas, Athanasios, Gottenberg, Jacques-Eric, Ramos-Casals, Manel, Dörner, Thomas, Ravaud, Philippe, Mariette, Xavier, Vitali, Claudio, Saraux, Alain, Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Rheumatology (Dep Rheumato - Malmo - SUEDE), Skåne University Hospital, Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), University Hospital Birmingham, Department of Pathophysiology, Medical School, University of Athens, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Autoimmune Diseases Josep Font Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Charité Hospital, Humboldt Universität zu Berlin, Sections of Rheumatology (Rheumatol - LECCO), Instituto San Giuseppe, Centre d'Investigation Clinique INSERM 1412 (CIC 1412 - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Humboldt-Universität zu Berlin, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: medicine.medical_specialty, Systemic disease, SYMPTOMS, MESH: Clinical Trials as Topic, MESH: Self Report, [SDV]Life Sciences [q-bio], ESSPRI, Immunology, Placebo-controlled study, Arthritis, Disease, PLACEBO-CONTROLLED TRIAL, Severity of Illness Index, Outcome measure, DOUBLE-BLIND, EUROPEAN LEAGUE, Internal medicine, MESH: Severity of Illness Index, Outcome Assessment, Health Care, medicine, Humans, Immunology and Allergy, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Pathological, MESH: Outcome Assessment (Health Care), DISEASE-ACTIVITY INDEX, DRY MOUTH, Clinical Trials as Topic, MESH: Humans, business.industry, PATIENT-REPORTED INDEX, Reproducibility of Results, RITUXIMAB TREATMENT, medicine.disease, OPEN-LABEL, Clinical trial, MESH: Reproducibility of Results, Peripheral neuropathy, MESH: Sjogren's Syndrome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sjogren's syndrome, Cohort, Physical therapy, Self Report, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ESSDAI
Abstract: Lymphocytic infiltration of different exocrine and non-exocrine epithelia is the pathological hallmark of primary Sjogren's syndrome, whereas involvement of salivary and lachrymal glands with the clinical counterpart of dry eye and dry mouth are the predominant features of the disease, together with fatigue and musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a consistent number of patients. As result, clinical features in SS can be divided into two facets: the benign subjective but disabling manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, great efforts have been made to develop valid tools for the assessment of these both facets. Disease specific questionnaires such as Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptom Inventory (SSI) have been proposed for evaluation of patients' symptoms, whereas different composite indexes have been suggested for the assessment of systemic disease activity. After that, an international project supported by EULAR, emerged to develop consensus disease activity indexes: the EULAR Sjogren's Syndrome Patients Reported Index (ESSPRI), and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic manifestations. Both EUIAR indexes have been developed in an international collaboration to be consensual. Both indices have now been validated in a large independent international cohort. They both have been shown to be feasible, valid and reliable instruments. Also, we have found that these two scores did not correlate, suggesting that these two indexes assess two different disease components that poorly overlap, but were complementary. The sensitivity to change of both scores has been assessed, they are both able to detect change, however, ESSDAI score, like other systemic score, is more sensitive to change than ESSPRI and other patient scores. Current work is ongoing to define disease activity levels and clinically important changes for defining significant clinical improvement with the systemic score ESSDAI, and ESSPRI. We hope that this increased knowledge on the way to assess patients with primary SS, along with the emergence of new targeted therapy, will put a great input in the improvement of conduction of clinical trials in pSS.. (C) 2013 Elsevier Ltd. All rights reserved.
Published: 2014

44. Validation of EULAR primary Sjogren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI)

Author: Seror, Raphaèle, Theander, Elke, Brun, Johan G, Ramos-Casals, Manel, Valim, Valeria, Dörner, Thomas, Bootsma, Hendrika, Tzioufas, Athanasios, Solans-Laqué, Roser, Mandl, Thomas, Gottenberg, Jacques-Eric, Hachulla, Eric, Sivils, Kathy L, Ng, Wan-Fai, Fauchais, Anne-Laure, Bombardieri, Stefano, Valesini, Guido, Bartoloni, Elena, Saraux, Alain, Tomsic, Matija, Sumida, Takayuki, Nishiyama, Susumu, Caporali, Roberto, Kruize, Aike A, Vollenweider, Cristina, Ravaud, Philippe, Vitali, Claudio, Mariette, Xavier, Bowman, Simon J, EULAR Sjögren's Task Force, Service de rhumatologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Department of Rheumatology, Lund University [Lund], Klinik für Dermatologie, Venerologie und Allergologie, Department of Pathophysiology, Medical School, University of Athens, Immuno-Rhumatologie Moléculaire, Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lille, Droit et Santé, University of Northumbria at Newcastle [United Kingdom], Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Department of Internal Medicine, Lupus Clinic, Sapienza University [Rome], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Faculty of Chemistry and Chemical Technology, University of Ljubjana, University of Tsukuba, Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Internal Medicine and section of Rheumatology, Villamarina Hospital, Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), University of Ljubljana, Université de Tsukuba = University of Tsukuba, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Translational Immunology Groningen (TRIGR)
Subjects: Male, [SDV]Life Sciences [q-bio], Sjögren's Syndrome, Severity of Illness Index, law.invention, RESPONSIVENESS, Randomized controlled trial, law, EUROPEAN LEAGUE, Immunology and Allergy, Prospective Studies, Disease Activity, Outcomes research, Non-U.S. Gov't, Prospective cohort study, Fatigue, primary Sjögren ’ s syndrome, Research Support, Non-U.S. Gov't, Middle Aged, 3. Good health, Europe, Sjogren's Syndrome, REPORTED INDEX, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Female, Adult, medicine.medical_specialty, Immunology, Pain, Research Support, CONTROLLED-TRIAL, Xerostomia, General Biochemistry, Genetics and Molecular Biology, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatology, Internal medicine, Severity of illness, Xerophthalmia, medicine, Journal Article, Humans, Validation Studies, RITUXIMAB, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Gold standard, Construct validity, Reproducibility of Results, HEALTH-STATUS INSTRUMENTS, medicine.disease, Physical therapy, Self Report, business, Rheumatism
Abstract: Objectives To validate the two recently developed disease activity indexes for assessment of primary Sjogren's syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI).Methods A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjogren's Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores.Results Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r= 0.59; ESSRPI with PGA: r= 0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores.Conclusions ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.
Published: 2014

45. Development of the ClinESSDAI : a clinical score without biological domain. A tool for biological studies

Author: Seror, Raphaèle, Meiners, Petra, Baron, Gabriel, Bootsma, Hendrika, Bowman, Simon J, Vitali, Claudio, Gottenberg, Jacques-Eric, Theander, Elke, Tzioufas, Athanasios, De Vita, Salvatore, Ramos-Casals, Manel, Dörner, Thomas, Quartuccio, Luca, Ravaud, Philippe, Mariette, Xavier, and EULAR Sjögren Task Force
Subjects: Journal Article, Validation Studies
Abstract: OBJECTIVE: To develop and validate ClinESSDAI (Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index), ie, ESSDAI without the biological domain. PATIENTS AND METHODS: The 702 fictive vignettes derived from 96 real cases of primary Sjögren's syndrome of the ESSDAI development study were used. As for ESSDAI development, the physician assessment of disease activity (0-10 scale) was used as the 'gold standard' in a multivariate model for weighting domains, after removing the biological domain. The reliability, assessed by intraclass correlation coefficient (ICC) between ClinESSDAI and ESSDAI, explored if ClinESSDAI was equivalent to ESSDAI. Its psychometric (ie, measurement) properties were compared with that of ESSDAI in an independent cohort. Also, its use was evaluated on data of two clinical trials. RESULTS: In multivariate modelling, all 11 domains remained significantly associated with disease activity, with slight modifications of some domain weights. Reliability between clinESSDAI and ESSDAI was excellent (ICC=0.98 and 0.99). Psychometric properties of clinESSDAI, disease activity levels and minimal clinically important improvement thresholds and its ability to detect change over time in clinical trials were very close to that of ESSDAI. CONCLUSIONS: ClinESSDAI appears valid and very close to the original ESSDAI. This score provides an accurate evaluation of disease activity independent of B-cell biomarkers. It could be used in various circumstances: (i) in biological/clinical studies to avoid data collinearity, (ii) in clinical trials, as secondary endpoint, to detect change independent of biological effect of the drug, (iii) in clinical practice to assess disease activity for visits where immunological tests have not been done.
Published: 2016

46. Effectiveness of vedolizumab for Crohn's disease with spondyloarthritis in fail with two TNF blocking agents

Author: Morel, Jacques, Constantin, Arnaud, Baron, Gabriel, Dernis, Emmanuelle, Flipo, Rene Marc, Rist, Stéphanie, Combe, Bernard, Gottenberg, Jacques Eric, Soubrier, Martin, Dougados, Maxime, Saraux, Alain, Ravaud, Philippe, Sibilia, Jean, Truchetet, Marie-Elise, Dublanc, Stéphanie, Barnetche, Thomas, Mariette, Xavier, Richez, Christophe, Blanco, Patrick, Mahler, Michael, Contin-Bordes, Cécile, Schaeverbeke, Thierry, Banse, Christopher, Armengol-Debeir, Laura, Vittecoq, Olivier, Université de Montpellier (UM), Service de rhumatologie, Centre Hospitalier Le Mans (CH Le Mans), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Médecine Interne, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lapeyronie [Montpellier] (CHU), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Physiologie, Les Hôpitaux Universitaires de Strasbourg (HUS)-Nouvel Hôpital Civil, Immunology and Allergy, University Hospital and School of Medicine, Université de Bordeaux (UB), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), INOVA Diagnostics, San Diego, CHU Bordeaux [Bordeaux], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Subjects: 030203 arthritis & rheumatology, 0301 basic medicine, medicine.medical_specialty, Crohn's disease, Blocking (radio), business.industry, [SDV]Life Sciences [q-bio], Treatment outcome, Follow up studies, Joint bone, medicine.disease, 3. Good health, Vedolizumab, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Rheumatology, Internal medicine, Physical therapy, medicine, Tumor necrosis factor alpha, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 5 aout 2017
Published: 2018

47. Non–TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug

Author: Gottenberg, Jacques, Brocq, Olivier, Perdriger, Aleth, Lassoued, Slim, Berthelot, Jean, Wendling, Daniel, Euller-Ziegler, Liana, Soubrier, Martin, Richez, Christophe, Fautrel, Bruno, Constantin, Arnaud L., Mariette, Xavier, Morel, Jacques, Gilson, Melanie, Cormier, Gregoire, Salmon, Jean, Rist, Stephanie, Lioté, Frederic, Marotte, Hubert, Bonnet, Christine, Marcelli, Marc, Sellam, Jeremie, Meyer, Olivier, Solau-Gervais, Elisabeth, Guis, Sandrine, Ziza, Jean, Zarnitsky, Charles, Chary-Valckenaere, Isabelle, Vittecoq, Olivier, Saraux, Alain, Pers, Yves-Marie, Gayraud, Martine, Bolla, Gilles, Claudepierre, Pascal, Ardizzone, Marc, Dernis, Emmanuelle, Breban, Maxime A., Fain, Olivier, Balblanc, Jean, Aberkane, Ouafaa, Vazel, Marion, Back, Christelle, Candon, Sophie, Chatenoud, Lucienne, Perrodeau, Elodie, Sibilia, Jean, Ravaud, Philippe, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, CHU Pontchaillou [Rennes], Rhumatologie, Centre Hospitalier Cahors, Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Université de Bordeaux (UB), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Politehnica of Bucharest [Romania] (UPB), INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire Sols et Environnement (LSE), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Laboratoire Traitement et Communication de l'Information (LTCI), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrative du Tissu Osseux (LBTO), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Psychopathologie Clinique, Langage et Subjectivité (LPCLS), Aix Marseille Université (AMU), Azienda Sanitaria Locale Viterbo, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche sur la Fusion par confinement Magnétique (IRFM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service de Rhumatologie - CH Le Havre, CH Le Havre, Service de Rhumatologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Rhumatologie [CHU de la Cavale-Blanche], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Unité clinique d'Immuno-Rhumatologie & Thérapeutique des maladies ostéo-articulaires, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Physiopathologie et Pharmacologie Clinique de la Douleur (LPPD), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Fakultät für Physik [Regensburg], Universität Regensburg (UR), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Centre hospitalier de Cahors-Centre hospitalier de Cahors, Centre Hospitalier Universitaire de Nice (CHU de Nice), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Biologie intégrative du tissu osseux, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM), Service de Rhumatologie - CHU Clermont Ferrand, CHU Clermont-Ferrand, Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Hôpital Lariboisière, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Service de rhumatologie [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor, Service de Rhumatologie [CHU Le Mans], CHU Le MAns, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Princesse Grace de Monaco ( CHPG ), Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire de Nice ( CHU de Nice ), Université de Bordeaux ( UB ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], University Politehnica of Bucharest [Romania] ( UPB ), Laboratoire Sols et Environnement ( LSE ), Institut National de la Recherche Agronomique ( INRA ) -Université de Lorraine ( UL ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Traitement et Communication de l'Information ( LTCI ), Télécom ParisTech-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques ( BIOSCAR ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Psychopathologie Clinique, Langage et Subjectivité ( LPCLS ), Aix Marseille Université ( AMU ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Recherche sur la Fusion par confinement Magnétique ( IRFM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Hôpital de la Cavale Blanche - CHRU Brest ( CHU - BREST ), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Physiopathologie et pharmacologie clinique de la douleur, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), University of Regensburg, Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), and Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: [ SDV.IMM ] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

48. Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study

Author: Nguyen, Minh Vu Chuong, Romand, Xavier, Trocme, Candice, Courtier, Anaïs, Marotte, Hubert, Thomas, Thierry, Miossec, Pierre, Tebib, Jacques, Grange, Laurent, Toussaint, Bertrand, Gaudin, Philippe, Nourisson, Cynthia, Soubrier, Martin, Mulliez, Aurelien, Baillet, Athan, Bardin, Thomas, Combe, Bernard, Dougados, Maxime, Flipo, René-Marc, Ravaud, Philippe, Tournadre, Anne, Derambure, C., Dzangue-Tchoupou, G., Bérard, C., Vergne, N., Hiron, M., D’Agostino, M., Musette, P., Lequerré, Thierry, Ruyssen-Witrand, Adeline, Degboé, Yannick, Cantagrel, Alain, Nigon, D., Lukas, C., Scaramuzzino, S, Allanore, Y., Schaeverbeke, Thierry, Morel, J., Sibilia, Jean, Cambon-Thomsen, A., Dieudé, P., Constantin, A, Nocturne, G., Virone, A., Ng, Wan-Fai, Le Guern, V., Hachulla, E., Cornec, D., Daien, C., Bienvenu, B., Marcelli, C., Wendling, D., Amoura, Z., Dhote, R., Lavigne, C., Fior, R., Gottenberg, Jacques-Eric, Seror, R., Mariette, Xavier, Eble, V., Legallicier, B., Joly, P., Caron, F., Tamion, F., Ducrotté, P., Lévesque, H., Ménard, J.-F., Jouen, F., Guerrot, D., Marié, I., D'Agostino, Maria-Antonietta, Wakefield, Richard, Berner-Hammer, Hilde, Vittecoq, Olivier, Filippou, Georgios, Bálint, Péter, Möller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Boers, Maarten, Gaillez, Corine, Van Holder, Karina, Le Bars, Manuela, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Rhumatologie [Saint-Etienne], Hôpital de Bellevue-CHU Saint-Etienne, Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of Immunogenomics, Mixed Unit HCL-BioMerieux, Hopital E. Herriot, Hospices Civils de Lyon (HCL), Service de Rhumatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Service de rhumatologie, CHU Clermont-Ferrand, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lapeyronie [Montpellier] (CHU), Service de rhumatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Laboratoire de Mathématiques Raphaël Salem (LMRS), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Toulouse [Toulouse], Service de rhumatologie et réadaptation fonctionelle, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Hôpital Purpan [Toulouse], Centre de rhumatologie, CHU Purpan, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Rhumatologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Avicenne [AP-HP], Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Service de Médecine Interne [CHU Rouen], Service de Néphrologie [Rouen], Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Unité de biostatistiques [CHU Rouen], Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Service de Dermatologie [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Academic Unit of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Chapel Allerton Hospital, Rheumatology Unit [Siena], National Institute of Rheumatology and Physiotherapy, Instituto Poal de Reumatologia, Barcelona, Università degli studi di Torino (UNITO), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Center for Rheumatology and Spine Diseases, Copenhagen (Center for Rheumatology and Spine Diseases), VU University Medical Center [Amsterdam], Epidemiology and Data Science, Rheumatology, AII - Inflammatory diseases, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Groupe de Recherche et d'Etudes du Processus Inflammatoire (GREPI), Université Joseph Fourier - Grenoble 1 (UJF), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Saint-Etienne-Hôpital de Bellevue, Délégation à la recherche clinique et aux innovations (DRCI), CHU de Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Service de rhumatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, CHU Cochin [AP-HP], Service de Rhumatologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [Rouen], Service d'Hépato-Gastroentérologie [Rouen], Unité de biostatistiques [Rouen], Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, fundacion Jimenez Diaz, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Università degli studi di Torino = University of Turin (UNITO), Service de Rhumatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Rhumatologie [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Hôpital Charles Nicolle [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel - EA 3886), Université d'Évry-Val-d'Essonne (UEVE), and Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne
Subjects: Male, Genetics and Molecular Biology (all), Settore MED/16 - REUMATOLOGIA, [SDV]Life Sciences [q-bio], DMARDs (biologic), Severity of Illness Index, Biochemistry, Arthritis, Rheumatoid, 0302 clinical medicine, Disease Activity, Rheumatoid Arthritis, Ultrasonography, Rheumatology, Immunology, Biochemistry, Genetics and Molecular Biology (all), Immunology and Allergy, Rheumatoid, 030212 general & internal medicine, Prospective Studies, skin and connective tissue diseases, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Synovitis, biology, Doppler, Middle Aged, 3. Good health, Europe, Treatment Outcome, Rheumatoid arthritis, Antirheumatic Agents, Combination, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, medicine.symptom, medicine.drug, musculoskeletal diseases, Adult, medicine.medical_specialty, General Biochemistry, Genetics and Molecular Biology, Abatacept, 03 medical and health sciences, Drug Therapy, Predictive Value of Tests, Internal medicine, medicine, Humans, Aged, 030203 arthritis & rheumatology, business.industry, Arthritis, C-reactive protein, Ultrasonography, Doppler, Joint effusion, Clinical and Epidemiological Research, medicine.disease, Methotrexate, biology.protein, Physical therapy, Joints, business, Rheumatism, Biomarkers
Abstract: Objectives To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naive patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). Methods In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology–European League Against Rheumatism (OMERACT–EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT–EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2–5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. Results Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2–5): −0.7 (95% CIs −1.2 to −0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. Conclusions In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. Trial registration number NCT00767325.
Published: 2016

49. X Chromosome Dose and Sex Bias in Autoimmune Diseases:Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome

Author: Liu, Ke, Kurien, Biji T, Zimmerman, Sarah L, Kaufman, Kenneth M, Taft, Diana H, Kottyan, Leah C, Lazaro, Sara, Weaver, Carrie A, Ice, John A, Adler, Adam J, Chodosh, James, Radfar, Lida, Rasmussen, Astrid, Stone, Donald U, Lewis, David M, Li, Shibo, Koelsch, Kristi A, Igoe, Ann, Talsania, Mitali, Kumar, Jay, Maier-Moore, Jacen S, Harris, Valerie M, Gopalakrishnan, Rajaram, Jonsson, Roland, Lessard, James A, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S, Huang, Andrew J W, Brennan, Michael T, Hughes, Pamela, Illei, Gabor G, Miceli-Richard, Corinne, Keystone, Edward C, Bykerk, Vivian P, Hirschfield, Gideon, Xie, Gang, Ng, Wan-Fai, Nordmark, Gunnel, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L, Rischmueller, Maureen, Rohrer, Michael, Segal, Barbara M, Vyse, Timothy J, Wahren-Herlenius, Marie, Witte, Torsten, Pons-Estel, Bernardo, Alarcon-Riquelme, Marta E, Guthridge, Joel M, James, Judith A, Lessard, Christopher J, Kelly, Jennifer A, Thompson, Susan D, Gaffney, Patrick M, Montgomery, Courtney G, Edberg, Jeffrey C, Kimberly, Robert P, Alarcón, Graciela S, Langefeld, Carl L, Gilkeson, Gary S, Kamen, Diane L, Tsao, Betty P, McCune, W Joseph, Salmon, Jane E, Merrill, Joan T, Weisman, Michael H, Wallace, Daniel J, Utset, Tammy O, Bottinger, Erwin P, Amos, Christopher I, Siminovitch, Katherine A, Mariette, Xavier, Sivils, Kathy L, Harley, John B, and Scofield, R Hal
Subjects: Gene dosage, Liver Cirrhosis, Sarcoidosis, Sex Chromosome Disorders of Sex Development, Case control study, Trisomy, Major clinical study, XXX, Article, Fluorescence, Chromosomes, Autoimmune Diseases, X chromosome, Systemic lupus erythematosus, Rheumatoid, Autoimmune disease, Prevalence, Live birth, Humans, Rheumatoid arthritis, Sex Distribution, Sex Chromosome Aberrations, In Situ Hybridization, Priority journal, Lupus Erythematosus, Fluorescence in situ hybridization, Arthritis, Systemic, Biliary, Quality control, Polymerase chain reaction, Single nucleotide polymorphism, Sjogren's Syndrome, Primary biliary cirrhosis, Sex chromosome aberration, Case-Control Studies, Female, Sex, Karyotype 47, Controlled study, Sex ratio, Human
Abstract: Objective More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ?1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. Methods All subjects in this study were female. We identified subjects with 47,XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47,XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. Results We found 47,XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47,XXX. There was an excess of 47,XXX among SLE and SS patients. Conclusion The estimated prevalence of SLE and SS in women with 47,XXX was ?2.5 and ?2.9 times higher, respectively, than that in women with 46,XX and ?25 and ?41 times higher, respectively, than that in men with 46,XY. No statistically significant increase of 47,XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. © 2016, American College of Rheumatology.
Published: 2016

50. Effectiveness and safety of abatacept in elderly patients with rheumatoid arthritis enrolled in the French Society of Rheumatology’s ORA registry

Author: Lahaye, Clément, Soubrier, Martin, Mulliez, Aurelien, Bardin, Thomas, Cantagrel, Alain, Combe, Bernard, Dougados, Maxime, Flipo, René-Marc, Le Loet, Xavier, Shaeverbeke, Thierry, Ravaud, Philippe, Mariette, Xavier, Gottenberg, Jacques-Eric, Society of Rheumatology, French, CHU Clermont-Ferrand, Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Sorbonne Paris Cité (USPC), Service de rhumatologie[Lille], Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de rhumatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de rhumatologie, CHU Bordeaux [Bordeaux], Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de rhumatologie [CHU Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Subjects: Adult, musculoskeletal diseases, safety, rheumatoid arthritis, medicine.medical_specialty, abatacept, effectiveness, Opportunistic Infections, Risk Assessment, Severity of Illness Index, elderly, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Severity of illness, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, Registries, Prospective cohort study, Adverse effect, Aged, 030203 arthritis & rheumatology, Aged, 80 and over, business.industry, Abatacept, Remission Induction, Age Factors, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Discontinuation, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, Antirheumatic Agents, Physical therapy, business, Immunosuppressive Agents, management, medicine.drug
Abstract: International audience; OBJECTIVE:To study the effect of age on the risk-benefit balance of abatacept in RA.METHODS:Data from the French orencia and RA registry, including a 2-year follow-up, were used to compare the effectiveness and safety of abatacept according to age.RESULTS:Among the 1017 patients, 103 were very elderly (⩾75 years), 215 elderly (65-74), 406 intermediate aged (50-64) and 293 very young (
Published: 2016

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