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1. Association between humoral serological markers levels and risk of SARS-CoV-2 infection after the primary COVID-19 vaccine course among ANRS0001S COV-POPART cohort participants

Author

Mathieu Chalouni, Paul Loubet, Edouard Lhomme, Laetitia Ninove, Benoit Barrou, Jean-Yves Blay, Maryvonne Hourmant, Jérome de Seze, Martine Laville, Bruno Laviolle, Jean-Daniel Lelièvre, Jacques Morel, Stéphanie Nguyen Quoc, Jean-Philippe Spano, Benjamin Terrier, Anne Thiebaut, Jean-Francois Viallard, François Vrtovsnik, Sophie Circosta, Aude Barquin, Mariam Gharib, Eric Tartour, Béatrice Parfait, Rodolphe Thiébaut, Laurence Meyer, Xavier de Lamballerie, Odile Launay, Linda Wittkop, and for the ANRS0001S COV-POPART study group

Subjects
Specific populations, SARS-CoV-2, Vaccine, Prediction, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background We assessed the prognostic value of serological humoral markers measured one month after the last dose of the primary COVID-19 vaccine course for predicting the risk of severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection over the following six months in specific populations. Methods ANRS0001SCOV-POPART is a French nationwide multicenter prospective observational cohort study assessing the immune response to Covid-19 vaccines routinely administered to 11 subgroups of patients with chronic disease and a control group. Participants from the ANRS0001S COV-POPART were included if they received at least two doses of Covid-19 vaccine for the primary vaccine course, had measurements of anti-Spike, anti-receptor binding domain (RBD) IgG-specific or neutralizing antibodies one month after the end of the primary vaccine course, without being infected by SARS-CoV-2 before the measurement. SARS-CoV-2 infections defined by a positive PCR/antigenic test or seroconversion to detectable anti nucleocapsid antibodies were evaluated until the first COVID-19 booster injection. Cox proportional hazards models taking into account interval-censored data were implemented to estimate the association between each antibody level and the risk of SARS-CoV-2 infection. Predictive performances were evaluated by the area under the receiving operating characteristic curve (AUROC). Results Two thousand five hundred seventy adults from a specific population and 1,123 from the control group were included. The cumulative probabilities of SARS-CoV-2 infections at five months after serological measurement were 6.0% 95% confidence interval: [5.0; 7.9] and 10.1% 95% confidence interval: [8.3; 11.9], respectively. Higher levels of anti-Spike IgG antibody were associated with a lower risk of SARS-CoV-2 infections in the control group, but not in the specific populations. Among the specific populations, AUROC were 74.5%, 74.9%, and 72.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. AUROC were superior in the specific populations, 82.0%, 81.2%, and 81.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. Conclusions Vaccine-induced antibody response after the primary course of Covid-19 infection only moderately discriminated between participants developing a SARS-CoV-2 infection during the Omicron wave. Trial registration NCT04824651 (first posted: 2021-04-01).

Published
2024
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2. Systematic screening for multimorbidities in patients with inflammatory rheumatic diseases enhanced preventive medication use and reduced hospitalisations: an exposed-non-exposed study

Author

Jacques Morel, Claire Immediato Daien, Vera Georgescu, Guillaume Decarriere, and Grégoire Mercier

Subjects
Medicine
Abstract

Rational Studies are needed to determine if multimorbidity screening and management reduce the rate of multimorbidity accumulation in patients with chronic inflammatory rheumatic diseases (IRD).Objectives This study evaluates the impact of systematic screening programme on patient care and hospitalisation rates.Methods Patients with IRD who participated in the screening programme (exposed patients) were identified within the French national health database and matched with controls. Two sets of analysis were performed: one with multivariate analysis and a second using a propensity score matching to ensure comparability between exposed patients and controls. The primary endpoint (PE) was a composite score assessing the dispensation of multimorbidity-preventing drugs, including vaccines, lipid-lowering agents, antiosteoporotic medications and antiplatelet drugs, during the year following the index date.Results The first analysis included 286 exposed patients and 858 controls, demonstrating a higher rate of meeting the PE in exposed patients (adjusted OR=1.6 (1.2–2.2), p

Published
2024
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3. Comparative early effectiveness across 14 PsA drugs and 5 classes of PsA treatment: 3-month results from the PRO-SPIRIT study

Author

Inmaculada de la Torre, Ennio Lubrano, Rieke Alten, Lars Erik Kristensen, Baojin Zhu, Dennis G McGonagle, Jacques Morel, Vinod Chandran, Marcus Ngantcha, William Tillett, Walid Fakhouri, Nicola Gullick, Khai Jing Ng, Àngels Martinez Ferrer, Dominika Kennedy, Thorsten Holzkämper, and Andris Kronbergs

Subjects
Medicine
Abstract

Background The psoriatic arthritis (PsA) Observational Study of Persistence of Treatment (PRO-SPIRIT) assesses effectiveness and persistence of real-world PsA treatments. Ixekizumab (IXE) is an interleukin (IL)-17A inhibitor (i) (IL-17Ai), approved for the treatment of adult PsA.Methods The aim of this predefined interim analysis was to report baseline characteristics along with early (3-month) descriptive and comparative real-world effectiveness in patients with PsA prescribed with advanced treatment including IL-17Ai; IXE or secukinumab (SEC), IL-12/23i, IL-23i, tumour necrosis factor (TNFi) or Janus kinase (JAKi).Results 1192 patients across 6 countries were analysed. At baseline, patients receiving IXE had longer disease duration and higher previous biological/targeted-synthetic disease-modifying antirheumatic drugs experience than patients starting TNFi and SEC 150, and less concomitant conventional-synthetic DMARD use than TNFi and JAKi. Comparative analyses at 3 months showed that: (a) versus TNFi, IXE exhibited similar improvement in clinical Disease Activity in PsA (cDAPSA) but significantly greater improvement in body surface area affected by psoriasis (BSA) and global assessments (physician GA, patient GA (PatGA)); (b) versus IL-12/23i and IL-23i (pooled), IXE showed significantly greater improvement in cDAPSA and PatGA; (c) IXE was as fast as JAKi in improving joint disease activity. Ad hoc analysis indicated that more patients with active psoriasis (BSA ≥3%) achieved minimal disease activity with IXE than JAKi or IL-12/23i. The responses to SEC varied by dosage.Conclusions This study confirms the rapid 3-month effectiveness of IXE on joint disease activity—as fast as TNFi and JAKi (cDAPSA), and exceeding IL-12/23i and IL-23i—along with clear benefits to skin.

Published
2024
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4. Persistence of power Doppler ultrasonography-detected synovitis over 1 year of follow-up predicts poor prognosis in rheumatoid arthritis in clinical remission: the SONORE prospective longitudinal study

Author

Bernard Combe, Nicolas Molinari, Jacques Morel, Gael Mouterde, Cédric Lukas, Nathalie Filippi, and Gregory Marin

Subjects
Medicine
Abstract

Objectives (1) To assess the progression of ultrasonography-detected synovitis in a cohort of patients with rheumatoid arthritis (RA) in remission during 1 year of follow-up (2) to evaluate the ability of consecutive examinations of ultrasonography to predict relapse (R) or radiographic progression (RP) at 1 year.Methods Patients with RA (2010 American College of Rheumatology-European Alliance of Associations for Rheumatology criteria) in clinical remission (Disease Activity Score in 28 joints (DAS28)0.6 or DAS28-CRP>3.2 and any modification of disease-modifying anti-rheumatic drugs or glucocorticoids defined relapse. Univariate and multivariate Cox regression analyses were used to evaluate factors associated with R/RP at 1 year.Results PDUS was detected in 75 (65.2%), 66, 60, 46 and 29 of the 115 patients with RA at baseline and at months 3, 6, 9 and 12, respectively. 58 (50.4%) patients exhibited persistent PDUS. After 1 year, 22/85 (25.9%) experienced relapse and 12 (14.1%) showed RP. On multivariate analysis, factors predicting R/RP at 1 year were persistent PDUS (HR=2.98, p=0.014) and an increase in DAS28-CRP level at the visit before relapse (HR=4.36, p=0.004).Conclusion Persistent PDUS during follow-up, rather than at baseline, predicted worse outcome at 1 year and requires careful monitoring.

Published
2024
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5. Long-range fiber-optic earthquake sensing by active phase noise cancellation

Author

Sebastian Noe, Dominik Husmann, Nils Müller, Jacques Morel, and Andreas Fichtner

Subjects
Medicine, Science
Abstract

Abstract We present a long-range fiber-optic environmental deformation sensor based on active phase noise cancellation (PNC) in metrological frequency dissemination. PNC sensing exploits recordings of a compensation frequency that is commonly discarded. Without the need for dedicated measurement devices, it operates synchronously with metrological services, suggesting that existing phase-stabilized metrological networks can be co-used effortlessly as environmental sensors. The compatibility of PNC sensing with inline amplification enables the interrogation of cables with lengths beyond 1000 km, making it a potential contributor to earthquake detection and early warning in the oceans. Using spectral-element wavefield simulations that accurately account for complex cable geometry, we compare observed and computed recordings of the compensation frequency for a magnitude 3.9 earthquake in south-eastern France and a 123 km fiber link between Bern and Basel, Switzerland. The match in both phase and amplitude indicates that PNC sensing can be used quantitatively, for example, in earthquake detection and characterization.

Published
2023
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6. Risk of severe infection associated with immunoglobulin deficiency under rituximab therapy in immune-mediated inflammatory disease

Author

Claire Rempenault, Bernard Combe, Jacques Morel, Philippe Guilpain, Cédric Lukas, Claire Immediato Daïen, and Léa Tardivon

Subjects
Medicine
Abstract

Objectives We evaluated the risk of severe infection in patients with immune-mediated inflammatory disease (IMID) treated with RTX and with Ig deficiency.Methods This was an observational, retrospective single-centre study of patients undergoing treatment with at least one rituximab (RTX) infusion for an IMID until 31 May 2020. Patients were followed up for at least 12 months after the last infusion or until severe infection or death. Ig deficiency was classified as prevalent (before RTX) or acquired (normal Ig assay results before RTX but Ig deficiency during a follow-up).Results Of 311 patients, 10.6% had prevalent and 19.6% acquired Ig deficiency. Prevalent Ig deficiency was related to concomitant treatment with glucocorticoids (GCs), in particular with a high daily dose at baseline; and acquired Ig deficiency to cumulative dose of RTX, mean Disease Activity Score in 28 joints (DAS28), immunosuppressor or GCs therapy at baseline, diabetes mellitus and obesity. Overall, 14.5% of patients had a severe infection during follow-up, which was numerically but not statistically more frequent in patients with prevalent Ig deficiency than normal Ig level. On multivariate analysis, risk of severe infection was associated with chronic pulmonary disease, GCs dose and mean DAS28-C reactive protein. In a time-dependent analysis, risk of severe infection was not associated with Ig deficiency, either acquired or prevalent (adjusted HR 1.04 (95% CI 0.5 to 2.3), p=0.92).Conclusion Risk of severe infection was not associated with RTX-induced Ig deficiency in patients with an IMID. RTX management should be discussed according to an individual assessment of the infectious risk, especially in patients with GC therapy or chronic lung disease.

Published
2024
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7. Hospitalizations for infections in primary Sjögren’s syndrome patients: a nationwide incidence study Severe infections in Sjögren’s syndrome

Author

Radjiv Goulabchand, Alain Makinson, Jacques Morel, Philine Witkowski-Durand-Viel, Nicolas Nagot, Paul Loubet, Camille Roubille, Danièle Noel, David Morquin, Kim Henry, Thibault Mura, and Philippe Guilpain

Subjects
Sjögren’s syndrome, infections, pneumonia, intestinal infections, mycobacteria, Medicine
Abstract

Background Primary Sjögren’s syndrome (pSS) is an autoimmune disease with increased risk of infections. Here, we assessed whether pSS patients were at higher risk of hospitalization for community and opportunistic infections.Methods We selected newly hospitalized pSS patients between 2011 and 2018, through a nationwide population-based retrospective study using the French Health insurance database. We compared the incidence of hospitalization for several types of infections (according to International Classification for Disease codes, ICD-10) between pSS patients and an age- and sex-matched (1:10) hospitalized control group. We calculated adjusted Hazard Ratios (aHR, 95% CI) adjusted on socio-economic status, past cardiovascular or lung diseases and blood malignancies factors.Results We compared 25 661 pSS patients with 252 543 matched patients. The incidence of hospitalizations for a first community infection was increased in pSS patients [aHR of 1.29 (1.22–1.31), p

Published
2022
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8. Occurrence of anterior uveitis in patients with spondyloarthritis treated with tumor necrosis factor inhibitors: comparing the soluble receptor to monoclonal antibodies in a large observational cohort

Author

Gisèle Khoury, Jacques Morel, Bernard Combe, and Cédric Lukas

Subjects
Spondyloarthritis, Psoriatic arthritis, Uveitis, TNF inhibitors, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background The objective of this study was to compare in real life the occurrence of anterior uveitis in patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA), treated with the soluble-receptor etanercept (ETA) or monoclonal antibodies (mAbs). Methods This was an observational, retrolective study. Patients with SpA who were prescribed anti-TNF agents between 2000 and 2014 were included. The risk of uveitis was interpreted qualitatively (number of subjects with at least one uveitis) and quantitatively (number of uveitis flares for each individual). Models were adjusted for propensity score of receiving preferentially mAbs or ETA. Results Four hundred twenty-nine patients were included (302 with SpA and 127 with PsA); 203 received a mAb and 226 ETA as a first TNF-α inhibitor. Probability of uveitis occurring during the first year of treatment was lower with ETA than with mAbs but not significantly (odds ratio 0.94 [95% confidence interval 0.35; 2.54], p = 0.90, on qualitative analysis and relative risk 0.62 [0.26; 1.46], p = 0.27, on quantitative analysis) after adjustment for the propensity score. The over-time risk of uveitis was numerically higher with ETA than with mAbs, but the differences were not statistically significant. Conclusion In this observational study, the risk of uveitis in patients with SpA does not appear to be greater with ETA than with mAb treatment. The occurrence of uveitis in patients receiving an anti-TNF-α agent seems linked more to the history of uveitis than the prescribed molecule.

Published
2020
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9. Predictors of good response to conventional synthetic DMARDs in early seronegative rheumatoid arthritis: data from the ESPOIR cohort

Author

Cédric Lukas, Julia Mary, Michel Debandt, Claire Daïen, Jacques Morel, Alain Cantagrel, Bruno Fautrel, and Bernard Combe

Subjects
Rheumatoid arthritis, Seronegative, ESPOIR cohort, DMARD, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background and objective Early seronegative rheumatoid arthritis (RA) is considered a specific entity, especially regarding diagnostic issues and prognosis. Little is known about its potentially different initial clinical presentation and outcome. We aimed to determine predictors of good response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in seronegative RA patients with early inflammatory arthritis. Patients and methods Patients from the ESPOIR cohort with early inflammatory arthritis fulfilling the 2010 ACR/EULAR classification criteria for RA despite negativity for both rheumatoid factor and anti-CCP antibodies. The primary endpoint was a good or moderate EULAR response assessed after 1 year of follow-up, given at least 3 months of treatment with a csDMARD. Secondary objectives were to compare the early therapeutic response to methotrexate (MTX) and leflunomide (LEF) versus other csDMARDs (hydroxychloroquine, sulfasalazine) and to identify factors associated with functional disability (Health Assessment Questionnaire-Disability Index [HAQ-DI] > 0.5 at 1 year) and structural progression (van der Heijde-modified total Sharp score > 1 and > 5 points at 1 year). Logistic regression analysis was used to determine independent predictors of outcomes. Results One hundred seventy-two patients were analyzed. Overall, 98/172 (57%) patients received MTX during the first year of follow-up. A good or moderate EULAR response at 1 year was associated with early use of csDMARDs (i.e., within 3 months after the first joint swelling) on univariate and multivariable analysis (odds ratio = 2.41 [95% confidence interval 1.07–5.42], p = 0.03). Response rates were not affected by other classical prognostic factors (i.e., baseline DAS28). Presence of erosions at baseline was associated with Sharp score progression > 1 point and > 5 points (both p = 0.03) at 1 year. HAQ-DI ≥ 1 at inclusion and active smoking were significantly associated with HAQ-DI > 0.5 at 1 year. Conclusion Our results suggest that delay in initiation of csDMARD more than baseline clinical, biological, or imaging features predominantly affects the outcome in early seronegative RA. These findings confirm that the usual therapeutic concepts in RA (early treatment, tight control, and treat-to-target) should be applied similarly to both seropositive and seronegative disease forms. Trial registration ClinicalTrials.gov: NCT03666091. Registered September 11, 2018.

Published
2019
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10. Outcome of patients with early arthritis without rheumatoid factor and ACPA and predictors of rheumatoid arthritis in the ESPOIR cohort

Author

Gaël Mouterde, Nathalie Rincheval, Cédric Lukas, Claire Daien, Alain Saraux, Philippe Dieudé, Jacques Morel, and Bernard Combe

Subjects
Rheumatoid arthritis, Early arthritis, Seronegative arthritis, Arthritis, ESPOIR cohort, Anti-citrullinated protein antibodies (ACPA), Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Objective To describe the disease course of patients with early arthritis without rheumatoid factor (RF) and anti-citrullinated protein auto-antibodies (ACPA) in an inception cohort. To determine baseline predictors of fulfilling 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) for these patients within 3 years. Method Patients included in the multicenter ESPOIR cohort were compared at baseline and 3 years by whether they were negative for RF and ACPA (“seronegative”) or positive for RF and/or ACPA (“seropositive”). Univariate analysis was used to determine the association between baseline variables in seronegative patients and RA classification. Stepwise multiple logistic regression was used to identify predictors of RA classification within 3 years, estimating odds ratios (ORs). Results Among 354 seronegative patients, 224/340 with available data (65.9%) fulfilled RA classification at baseline and 189/233 (81.1%) at 3 years. As compared with seropositive patients, seronegative patients had lower DAS28 (p = 0.002) and lower modified total Sharp score (mTSS; p = 0.026) at baseline; DAS28 remission was similar (p = 0.634), but radiographic progression rate was lower in seronegative patients (p

Published
2019
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11. The prevalence of ACPA is lower in rheumatoid arthritis patients with an older age of onset but the composition of the ACPA response appears identical

Author

Debbie M. Boeters, Lukas Mangnus, Sofia Ajeganova, Elisabet Lindqvist, Björn Svensson, René E. M. Toes, Leendert A. Trouw, Tom W. J. Huizinga, Francis Berenbaum, Jacques Morel, Solbritt Rantapää-Dahlqvist, and Annette H. M. van der Helm-van Mil

Subjects
Rheumatoid arthritis, Age, Autoantibodies, ACPA characteristics, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Rheumatoid arthritis (RA) consists of two syndromes, one autoantibody-positive and one autoantibody-negative. Existing data on the relation between age of onset and prevalence of autoantibodies were conflicting. Therefore this multicohort study assessed the age of onset in relation to the presence of autoantibodies. The association with characteristics of the anti-citrullinated protein antibodies (ACPA) response was also explored. Methods The 1987 criteria-positive RA patients included in the Leiden EAC, BARFOT, ESPOIR, Umeå and Lund cohorts (n = 3321) were studied at presentation for age of onset and the presence of ACPA, rheumatoid factor (RF) and anti-carbamylated protein (anti-CarP) antibodies. Logistic regression analyses were performed; effect sizes were summarized in inverse-weighted meta-analyses. Within ACPA-positive RA, ACPA level was studied in all cohorts; ACPA isotypes, ACPA fine specificity and ACPA avidity index and clinical characteristics were studied in the Leiden EAC. Results From the age of 50 onward, the proportion of ACPA-negative RA patients increased with age in the five cohorts. Similar observations were made for RF and anti-CarP. The composition of the ACPA response did not change with increasing age of onset with respect to titer, isotype distribution, fine specificity and avidity index. With increasing age of onset, RA patients smoked less often, had higher acute phase reactants and more often had a sub(acute) symptom onset. Conclusions Data of five cohorts revealed that with older age of onset ACPA-negative RA is more frequent than ACPA-positive RA, while characteristics of ACPA-positive RA as judged by the composition of the ACPA response appeared not age dependent. Further biologic studies are needed to characterize the pathogenesis of ACPA-negative polyarthritis at older age and to promote personalized treatment decisions in ACPA-negative patients in daily practice.

Published
2017
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12. APRIL Induces a Novel Subset of IgA+ Regulatory B Cells That Suppress Inflammation via Expression of IL-10 and PD-L1

Author

Cynthia M. Fehres, Nathalie O. van Uden, Nataliya G. Yeremenko, Leticia Fernandez, Gabriela Franco Salinas, Leonie M. van Duivenvoorde, Bertrand Huard, Jacques Morel, Hergen Spits, Michael Hahne, and Dominique L. P. Baeten

Subjects
APRIL, Immunoregulation, IgA, IL-10, inflammation, regulatory B cells, Immunologic diseases. Allergy, RC581-607
Abstract

Regulatory B cells (Bregs) are immunosuppressive cells that modulate immune responses through multiple mechanisms. The signals required for the differentiation and activation of these cells remain still poorly understood. We have already shown that overexpression of A PRoliferation-Inducing Ligand (APRIL) reduces the incidence and severity of collagen-induced arthritis (CIA) in mice. Furthermore, we have described that APRIL, but not BAFF, promoted IL-10 production and regulatory functions in human B cells. Therefore, we hypothesized that APRIL, but not BAFF, may be involved in the induction and/or activation of IL-10 producing Bregs that suppress inflammatory responses in vitro and in vivo. Here, we describe that APRIL promotes the differentiation of naïve human B cells to IL-10-producing IgA+ B cells. These APRIL-induced IgA+ B cells display a Breg phenotype and inhibit T cell and macrophage responses through IL-10 and PD-L1. Moreover, APRIL-induced IL-10 producing Bregs suppress inflammation in vivo in experimental autoimmune encephalitis (EAE) and contact hypersensitivity (CHS) models. Finally, we showed a strong correlation between APRIL and IL-10 in the inflamed synovial tissue of inflammatory arthritis patients. Collectively, these observations indicate the potential relevance of this novel APRIL-induced IgA+ Breg population for immune homeostasis and immunopathology.

Published
2019
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13. Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's Syndrome

Author

Armen Sanosyan, Claire Daien, Anaïz Nutz, Karine Bollore, Anne-Sophie Bedin, Jacques Morel, Valérie Zimmermann, Gaetane Nocturne, Marianne Peries, Nicolas Guigue, Jacques-Eric Gottenberg, Philippe Van de Perre, Xavier Mariette, and Edouard Tuaillon

Subjects
primary Sjögren's syndrome, Epstein-Barr virus, anti-EA antibodies, EBV DNA, beta-2 microglobulin, autoantibodies, Immunologic diseases. Allergy, RC581-607
Abstract

Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivation, production of autoantibodies and increased risk of B cell lymphomas. Serological profile of Epstein-Barr virus (EBV) reactivation and increase EBV DNA levels in exocrine glands are observed in pSS, but whether these abnormalities are accompanied with disturbed systemic EBV control or have any association with pSS activity remains to be investigated. In this observational study, we initially explored anti-EBV antibodies and cell-free DNA in 395 samples from a cross-sectional plasma collection of pSS patients included in ASSESS French national cohort. Results were assessed in relation with disease activity. Further, to assess cell-associated EBV DNA we organized a case-control study including 20 blood samples from pSS patients followed in University Hospital Center of Montpellier. Results were compared with matched controls. Robust response against EBV early antigen (EA) was observed in pSS patients with anti-SSA/B (Sjögren's syndrome A and B) and anti-SSA autoantibodies compared to anti-SSA/B negatives (P < 0.01 and P = 0.01, respectively). Increased beta-2 microglobulin, kappa and lambda light chains, and immunoglobulin G levels were more frequently observed in anti-EA seropositive pSS subjects compared to anti-EA negative subjects (P < 0.001; P = 0.001; P = 0.003, respectively). Beta-2 microglobulin was independently associated with anti-EA positivity in multivariate analysis (P < 0.001). Plasma cell-free EBV DNA and EBV cellular reservoir was not different between pSS patients and controls. We conclude that serological evidence of EBV reactivation was more frequently observed and more strongly associated with anti-SSA/B status and B cell activation markers in pSS. However, serological profile of EBV reactivation was not accompanied by molecular evidence of systemic EBV reactivation. Our data indicated that EBV infection remains efficiently controlled in the blood of pSS patients.

Published
2019
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14. Intriguing Relationships Between Cancer and Systemic Sclerosis: Role of the Immune System and Other Contributors

Author

Alexandre Thibault Jacques Maria, Léo Partouche, Radjiv Goulabchand, Sophie Rivière, Pauline Rozier, Céline Bourgier, Alain Le Quellec, Jacques Morel, Danièle Noël, and Philippe Guilpain

Subjects
Systemic sclerosis (scleroderma), cancer, immunosurveillance, paraneopastic syndrome, immunoediting of cancer, autoimmunity, Immunologic diseases. Allergy, RC581-607
Abstract

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder, characterized by multisystem involvement, vasculopathy, and fibrosis. An increased risk of malignancy is observed in SSc (including breast and lung cancers), and in a subgroup of patients with specific autoantibodies (i.e., anti-RNA polymerase III and related autoantibodies), SSc could be a paraneoplastic syndrome and might be directly related to an immune response against cancer. Herein, we reviewed the literature, focusing on the most recent articles, and shed light onto the potential relationship between cancer and scleroderma regarding temporal and immunological dimensions.

Published
2019
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15. IL-10 Producing B Cells Ability to Induce Regulatory T Cells Is Maintained in Rheumatoid Arthritis

Author

Julie Mielle, Rachel Audo, Michael Hahne, Laurence Macia, Bernard Combe, Jacques Morel, and Claire Daien

Subjects
regulatory B cell, autoimmunity, interleukin 10, programmed death-ligand 2, rheumatoid arthritis, B10, Immunologic diseases. Allergy, RC581-607
Abstract

Despite growing evidence highlighting the relevance of increasing IL-10-producing B cells (B10+cells) in autoimmune diseases, their functions in patients are still unknown. The aim of this study was to evaluate the functions of CpG-induced B10+ cells isolated from healthy controls (HC) and rheumatoid arthritis (RA) patients, on naïve T cell differentiation. We demonstrated that CpG-induced B10+ cells from HC drove naïve T cell differentiation toward regulatory T cells (Treg cells) and IL-10-producing T cells (Tr1) through IL-10 secretion and cellular contacts. B10+ cells from HC did not decrease T helper 1 (Th1) nor and tumor necrosis factor α producing T cell (TNFα+ T cell) differentiation. We showed that in RA, B10+ cells could also induce Treg cells and Tr1 from naïve T cells. Contrary to HC, B10+ cells from RA patients increased naïve T cell conversion into Th1. Interestingly, PD-L2, a programmed death-1 (PD-1) ligand that inhibits PD-L1 and promotes Th1 differentiation, was overexpressed on RA B10+ cells compared to HC B10+ cells. Together, our findings showed that CpG-induced B10+ cells may be used to increase Treg cells in patients with RA. However, CpG may not be the most adequate stimuli as CpG-induced B10+ cells also increased inflammatory T cells in those patients.

Published
2018
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16. PhosphoLipid transfer protein (PLTP) exerts a direct pro-inflammatory effect on rheumatoid arthritis (RA) fibroblasts-like-synoviocytes (FLS) independently of its lipid transfer activity.

Author

Rachel Audo, Valérie Deckert, Claire I Daien, Hélène Che, Jamila Elhmioui, Stéphanie Lemaire, Jean-Paul Pais de Barros, Catherine Desrumaux, Bernard Combe, Michael Hahne, Laurent Lagrost, and Jacques Morel

Subjects
Medicine, Science
Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease with modification of lipids profile and an increased risk of cardiovascular events related to inflammation. Plasma phospholipid transfer protein (PLTP) exerts a lipid transfer activity through its active form. PLTP can also bind to receptors such as ATP-binding cassette transporter A1 (ABCA1). In addition to its role in lipoprotein metabolism and atherosclerosis, the latest advances came in support of a complex role of PLTP in the regulation of the inflammatory response, both with pro-inflammatory or anti-inflammatory properties. The aim of the present study was to decipher the role of PLTP in joint inflammation and to assess its relevance in the context of RA. PLTP expression was examined by western-blot and by immunochemistry. ABCA1 expression was analyzed by flow cytometry. Lipid transfer activity of PLTP and pro-inflammatory cytokines were measured in sera and synovial fluid (SF) from RA patients and controls (healthy subjects or osteoarthritis patients [OA]). FLS were treated with both lipid-transfer active form and inactive form of recombinant human PLTP. IL-8, IL-6, VEGF and MMP3 produced by FLS were assessed by ELISA, and proliferation by measuring 3H-Thymidine incorporation. RA synovial tissues showed higher PLTP staining than OA and PLTP protein levels were also significantly higher in RA-FLS. In addition, RA, unlike OA patients, displayed elevated levels of PLTP activity in SF, which correlated with pro-inflammatory cytokines. Both lipid-transfer active and inactive forms of PLTP significantly increased the production of cytokines and proliferation of FLS. ABCA1 was expressed on RAFLS and PLTP activated STAT3 pathway. To conclude, PLTP is highly expressed in the joints of RA patients and may directly trigger inflammation and FLS proliferation, independently of its lipid transfer activity. These results suggest a pro-inflammatory role for PLTP in RA.

Published
2018
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17. Phosphatidylserine Outer Layer Translocation Is Implicated in IL-10 Secretion by Human Regulatory B Cells.

Author

Rachel Audo, Charlotte Hua, Michael Hahne, Bernard Combe, Jacques Morel, and Claire I Daien

Subjects
Medicine, Science
Abstract

B cells can have a regulatory role, mainly mediated by interleukin 10 (IL-10). IL-10 producing B cells (B10 cells) cells remain to be better characterized. Annexin V binds phosphatidylserine (PS), which is externalized during apoptosis. Previous works suggested that B10 cells are apoptotic cells since they bind Annexin V. Others showed that Annexin V binding could also be expressed on viable B cells. We aimed to explore if PS exposure can be a marker of B10 cells and if PS exposure has a functional role on B cell IL-10 production in healthy subjects. We found that B10 cells were significantly more often Annexin V+ than IL-10 non-producing B cells. After CpG activation, Annexin V+ B cells differentiated more often into B10 cells than Annexin Vneg B cells. Cell death and early apoptosis were similar between Annexin V+ and Annexin Vneg B cells. PS blockage, using biotinylated AnV and glyburide, decreased B10 cell differentiation. This study showed that B10 cells have an increased PS exposure independently of any apoptotic state. B cells exposing PS differentiate more into B10 cells whereas PS blockage inhibits B10 cells generation. These results strongly suggest a link between PS exposure and B10 cells.

Published
2017
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18. Sodium excretion is higher in patients with rheumatoid arthritis than in matched controls.

Author

Sarah Marouen, Guilhem du Cailar, Rachel Audo, Cedric Lukas, Gaelle Vial, Anne Tournadre, Emmanuel Barrat, Jean Ribstein, Bernard Combe, Jacques Morel, and Claire I Daien

Subjects
Medicine, Science
Abstract

It was shown that sodium can promote auto-immunity through the activation of the Th17 pathway. We aimed to compare sodium intake in patients with rheumatoid arthritis (RA) vs. matched controls.This case-control study included 24 patients with RA at diagnosis and 24 controls matched by age, gender and body mass index. Sodium intake was evaluated by 24-hr urinary sodium excretion.Sodium excretion was greater for patients with early RA (2,849±1,350 vs. 2,182±751.7mg/day, p = 0.039) than controls. This difference remained significant after adjustment for smoking and the use of anti-hypertensive and nonsteroidal anti-inflammatory drugs (p = 0.043). Patients with radiographic erosion at the time of diagnosis had a higher sodium excretion than those without (p = 0.028).Patients with early RA showed increased sodium excretion which may have contributed to autoimmunity.

Published
2017
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19. Which and How Many Patients Should Be Included in Randomised Controlled Trials to Demonstrate the Efficacy of Biologics in Primary Sjögren's Syndrome?

Author

Valérie Devauchelle-Pensec, Jacques-Eric Gottenberg, Sandrine Jousse-Joulin, Jean-Marie Berthelot, Aleth Perdriger, Eric Hachulla, Pierre Yves Hatron, Xavier Puechal, Véronique Le Guern, Jean Sibilia, Laurent Chiche, Vincent Goeb, Olivier Vittecoq, Claire Larroche, Anne Laure Fauchais, Gilles Hayem, Jacques Morel, Charles Zarnitsky, Jean Jacques Dubost, Philippe Dieudé, Jacques Olivier Pers, Divi Cornec, Raphaele Seror, Xavier Mariette, Emmanuel Nowak, and Alain Saraux

Subjects
Medicine, Science
Abstract

OBJECTIVE:The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjögren's syndrome (pSS). METHODS:We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo. RESULTS:We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study. CONCLUSION:This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point.

Published
2015
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20. Predictive Factors of Response to Biological Disease Modifying Antirheumatic Drugs: Towards Personalized Medicine

Author

Claire I. Daïen and Jacques Morel

Subjects
Pathology, RB1-214
Abstract

Many therapies are now available for patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate including tumor necrosis factor inhibitors, abatacept, tocilizumab, and rituximab. Clinical response to drugs varies widely between individuals. A part of this variability is due to the characteristics of the patient such as age, gender, concomitant therapies, body mass index, or smoking status. Clinical response also depends on disease characteristics including disease activity and severity and presence of autoantibodies. Genetic background, cytokine levels, and immune cell phenotypes could also influence biological therapy response. This review summarizes the impact of all those parameters on response to biological therapies.

Published
2014
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21. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjögren's syndrome. Data at enrollment in the prospective ASSESS cohort.

Author

Jacques-Eric Gottenberg, Raphaèle Seror, Corinne Miceli-Richard, Joelle Benessiano, 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, Xavier Puéchal, Stephanie Rist, Alain Saraux, Damien Sene, Jean Sibilia, Olivier Vittecoq, Gaétane Nocturne, Philippe Ravaud, and Xavier Mariette

Subjects
Medicine, Science
Abstract

To analyze the clinical and immunological characteristics at enrollment in a large prospective cohort of patients with primary Sjögren's syndrome (pSS) and to investigate the association between serum BAFF, beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment.Three hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the "Assessment of Systemic Signs and Evolution of Sjögren's Syndrome" (ASSESS) 5-year prospective cohort. At enrollment, serum markers were assessed as well as activity of the disease measured with the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).Patient median age was 58 (25(th)-75(th): 51-67) and median disease duration was 5 (2-9) years. Median ESSDAI at enrollment was 2 (0-7) with 30.9% of patients having features of systemic involvement. Patients with elevated BAFF, beta2-microglobulin and kappa, lambda FLCS had higher ESSDAI scores at enrollment (4 [2]-[11] vs 2 [0-7], P = 0.03; 4 [1]-[11] vs 2 [0-7], P< 0.0001); 4 [2]-[10] vs 2 [0-6.6], P< 0.0001 and 4 [2-8.2] vs 2 [0-7.0], P = 0.02, respectively). In multivariate analysis, increased beta2-microglobulin, kappa and lambda FLCs were associated with a higher ESSDAI score. Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma (1173.3(873.1-3665.5) vs 898.9 (715.9-1187.2) pg/ml, P = 0.01 and 2.6 (2.2-2.9) vs 2.1 (1.8-2.6) mg/l, P = 0.04, respectively).In pSS, higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity.

Published
2013
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23. Measurement of the magnetic field profile in the atomic fountain clock FoCS-2 using Zeeman spectroscopy

Author

Laurent, Devenoges, Gianni, Di Domenico, André, Stefanov, Antoine, Jallageas, Jacques, Morel, Thomas, Südmeyer, and Pierre, Thomann

Subjects
Physics - Atomic Physics
Abstract

We report the evaluation of the second order Zeeman shift in the continuous atomic fountain clock FoCS-2. Because of the continuous operation and of its geometrical constraints, the methods used in pulsed fountains are not applicable. We use here time-resolved Zeeman spectroscopy to probe the magnetic field profile in the clock. The pulses of ac magnetic excitation allow us to spatially resolve the Zeeman frequency and to evaluate the Zeeman shift with a relative uncertainty smaller than 10E-16., Comment: 7 pages, 10 figures

Published
2016

24. Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study

Author

Lucas Guillo, Benoit Flachaire, Jérôme Avouac, Catherine Dong, Maria Nachury, Guillaume Bouguen, Anthony Buisson, Ludovic Caillo, Mathurin Fumery, Cyrielle Gilletta, Xavier Hébuterne, Pierre Lafforgue, David Laharie, Emmanuel Mahé, Hubert Marotte, Stéphane Nancey, Sébastien Ottaviani, Jean-Hugues Salmon, Guillaume Savoye, Mélanie Serrero, Mathieu Uzzan, Manuelle Viguier, Christophe Richez, Laurent Peyrin-Biroulet, Philipe Seksik, Thao Pham, Philippe Ah-Soune, Nadia Arab, Laurent Beaugerie, Loïs Bolko, Joelle Bonnet, Yoram Bouhnik, Anne Bourrier, Franck Brazier, Franck Carbonnel, Maeva Charkaoui, Isabelle Charlot-Lambrecht, Antoine Chupin, Alice Combier, Marion Couderc, Fabienne Coury-Lucas, Ariadne Desjeux, Nicolas Duveau, Anne Grasland, Jean-Charles Grimaud, Xavier Guennoc, Cécilia Landman, Isabelle Nion-Larmurier, Catherien Leberre, Romain Leenhardt, Aude Le Goffic, Henri Montaudie, Jacques Morel, Thierry Passeron, Jeanne-Marie Perotin Collard, Elodie Poisnel, Vincent Pradel, Martin Soubrier, Harry Sokol, Eric Toussirot, Caroline Trang, My-Linh Trans Minh, Sophie Trijau, Frank Verhoeven, Stéphanie Viennot, Daniel Wendling, Hôpital Nord [CHU - APHM], Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut du Mouvement et de l’appareil Locomoteur [Hôpital Sainte-Marguerite - APHM] (IML), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Victor Dupouy, Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), 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), Hospices Civils de Lyon (HCL), 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Vieillissement, Fragilité (VIEFRA - EA 3797), Université de Reims Champagne-Ardenne (URCA), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Beaujon [AP-HP], Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Hôpital universitaire Robert Debré [Reims], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), 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), and Hôpital Charles Nicolle [Rouen]-CHU Rouen

Subjects
Adult, Cohort Studies, Immunomodulating Agents, Crohn Disease, Immune-mediated inflammatory diseases, Hepatology, Gastroenterology, Humans, Tumor Necrosis Factor Inhibitors, Ustekinumab, Molecular targeted therapy, Combination therapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.

Published
2023

26. Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation that are reversed by inflammation control

Author

Rachel Audo, Pauline Sanchez, Benjamin Rivière, Julie Mielle, Jian Tan, Cédric Lukas, Laurence Macia, Jacques Morel, Claire Immediato Daien, MORNET, Dominique, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), and The University of Sydney

Subjects
rheumatoid arthritis, [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, Rheumatology, microbiota, gut permeability, Pharmacology (medical), DMARDs, gut homeostasis
Abstract

Objective To assess how RA and DMARDs affect gut permeability. Methods To explore colonic mucosa integrity, tight junction proteins zonula occludens-1, occludin and claudin 2 were quantified by immunohistochemistry on colonic biopsies in 20 RA patients and 20 age- and sex-matched controls. Staining intensity was assessed by two blinded independent readers. To explore intestinal permeability, serum concentrations of lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and zonulin-related proteins (ZRPs) were evaluated by ELISA in another cohort of 59 RA patients: 21 patients naive for DMARDs [17 before and after introduction of a conventional synthetic DMARD (csDMARD)], 38 patients with severe RA [before and after introduction of a biological DMARD (bDMARD)] and 33 healthy controls. Results Z0-1 protein was less expressed in the colon of RA patients than controls [mean score 1.6 (s.e.m. 0.56) vs 2.0 (0.43), P = 0.01], while no significant difference was detected for occludin and claudin-2. RA patients had higher serum LBP and sCD14 concentrations than controls. LBP and sCD14 levels were significantly correlated with the 28-joint DAS (r = 0.61, P = 0.005 and r = 0.57, P = 0.01, respectively) while ZRP did not. bDMARD responders had significantly reduced LBP and sCD14 concentrations, unlike bDMARD non-responders and patients treated with csDMARDs. Conclusion RA patients have altered colonic tight junction proteins and increased serum biomarkers of intestinal permeability. There was a correlation between serological markers of intestinal permeability and disease activity as well as bDMARD response. These results suggest a link between impaired gut integrity and systemic inflammation in RA.

Published
2022

29. P184 A 24-month prospective psoriatic arthritis observational study of persistence of treatment - interim analysis of baseline characteristics

Author

Jacques Morel, Lorenzo Dagna, Beatriz Joven Ibañez, Thorsten Holzkaemper, Celine El Baou, Leonore Unger, Angelo Semeraro, Nicola Gullick, and Tamas Treuer

Subjects
Rheumatology, Pharmacology (medical)
Abstract

Background/Aims Ixekizumab (ixe), a highly selective interleukin (IL)-17A monoclonal antibody, has been approved for treatment of psoriatic arthritis (PsA). However, there is limited real-world evidence (RWE) available for ixe. PRO-SPIRIT is the first large-sample prospective observational study to provide RWE for ixe in patients (pts) with PsA. PRO-SPIRIT’s primary objective is to describe treatment persistence at 24 months (M) among pts with PsA who initiate or switch to a new biologic Disease-Modifying Arthritis Rheumatic Drugs (bDMARDs) or targeted synthetic (tsDMARDs), including ixe. This abstract describes the interim baseline (BL) characteristics. Methods PRO-SPIRIT is a prospective observational study, conducted in FR, ES, IT, DE, UK, and CA, enrolling adults with PsA (≥6M) to be initiated or switched to a new b/tsDMARD, locally approved for PsA. Treatment groups include ixe, secukinumab, IL-12/IL-23 inhibitors (i) (ustekinumab) or IL-23i (guselkumab), tumour necrosis factor (TNFi) (adalimumab, etanercept, infliximab or biosimilar), Janus kinase (JAKi) (tofacitinib or upadacitinib). Pt demographic, disease activity and therapy characteristics are collected at BL; clinical and patient-reported outcomes measures are collected at BL and at a routine post-BL visit. BL descriptive statistics are reported. Results From December 2019 until this interim data cut (June 2021), a total of 477 pts (305 female; mean age 52) were enrolled. Mean age ranged from 48 (IL-12/23i and IL-23i) to 55 (JAKi), with a majority of female pts in each group. Pts in the IL-12/23i and IL-23i and TNFi groups showed the shortest time since PsA diagnosis (5.2±4.5; 6.5±7.9), while pts in the JAKi group showed the longest time (10.6±9.4). The lowest proportion of pts with a prior b/tsDMARDs use was observed in the TNFi group (31%), the highest in the IL-12/23i and IL-23i group (71%). Pts in the ixe and IL-12/23i and IL-23i groups were more likely to be on monotherapy. Tender Joint Count (9.1-11.3) and Swollen Joint Count (3.3-5.8) were comparable across groups, with the highest values in the ixe and JAKi groups, respectively. Pt proportion with enthesitis and dactylitis was higher in the ixe, secukinumab and JAKi groups. Percentage of Body Surface Area affected by psoriasis was higher in the ixe, secukinumab and IL-12/23i and IL-23i groups. Pt proportion with nail psoriasis was higher in the ixe and secukinumab groups. Physician's Global Assessment Visual Analog Scale (VAS), Patient’s Global Assessment VAS and Patient's Assessment of Joint Pain VAS reflected a high burden of illness. Conclusion The reported BL characteristics offer preliminary information about which pts initiate or switch to a b/tsDMARD in a real-life setting. Future disclosures (at 12 and 24M) will provide RWE regarding persistence, effectiveness, and healthcare resource use of available treatments for PsA, which will help pts and physicians to make better informed treatment decisions. Disclosure J. Morel: Consultancies; J. Morel has been a speaker and/or consultant for: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Eli Lilly and Company, Fresenius, Galapagos, Glaxo Smith Kline, Médac, Novartis, Sandoz, and Sanofi. Grants/research support; J. Morel has received grant funding/research support from: Biogen, Bristol Myers Squibb, Eli Lilly and Company, Novartis, and Pfizer. L. Dagna: Consultancies; L. Dagna has been a speaker and/or consultant for: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Celltrion, Lilly, Galapagos, GSK, Janssen, Kiniska, Pfizer, Roche, Sobi, and Sanofi. B. Ibañez: Grants/research support; B. Joven-Ibáñez has been a speaker for and has received grant funding/research support from: Eli Lilly and Company. T. Holzkaemper: Shareholder/stock ownership; T. Holzkaemper is a shareholder and employee of: Eli Lilly and Company. C. El Baou: Consultancies; C. El Baou has worked as a consultant for: Eli Lilly and Company. L. Unger: Other; L. Unger has been a speaker for: Eli Lilly and Company. A. Semeraro: None. N. Gullick: Consultancies; N. Gullick has been a speaker and/or consultant for: AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, and UCB. Grants/research support; N. Gullick has received grant funding/research support from: AbbVie, AstraZeneca, Eli Lilly and Company, Izana, and Novartis. T. Treuer: Shareholder/stock ownership; T. Truer is a shareholder and employee of: Eli Lilly and Company.

Published
2023

30. Triggered Seismicity in a Flooded Former Coal Mining Basin (Gardanne Area, France)

Author

Pascal Dominique, Hideo Aochi, and Jacques Morel

Subjects
Geotechnical Engineering and Engineering Geology, Water Science and Technology
Abstract

We studied the correlation between seismicity and the water table level in an abandoned coal mine (Bouches-du-Rhône, France), closed in 2003, where groundwater has been pumped out since 2010 to prevent underground flooding. Microseismicity was first felt by the population in 2010 and a strongly felt seismic swarm occurred in November 2012. The origin of the seismicity was therefore questioned, in relation to both the potential instability of old, shallow galleries that might generate damage at the surface and a local seismic hazard assessment. A temporary dense seismic network in the area allowed us to analyse the spatial distribution of the seismicity in detail. Most of the seismicity was clearly located under the mine workings, highlighting that an existing fault system crossing the mining operation was being hydraulically activated, in accordance with the known tectonic extension regime. Our analysis clearly shows a spatiotemporal relationship between seismic migration and the level of the mine aquifer between 2013 and 2017. Thus, seismicity will persist with oscillations of the mining aquifer, depending on the pumping capacities and effective rainfall. Continuous hydraulic and seismic monitoring is necessary to better understand these phenomena and assess the associated risks.

Published
2022

32. Concomitant fibromyalgia in primary Sjögren's syndrome in the French ASSESS cohort: comparison of the ACR 1990 and ACR 2016 criteria, FiRST questionnaire and physician's opinion

Author

Jean-Jacques, Dubost, Marion, Couderc, Bruno, Pereira, Xavier, Mariette, Raphaèle, Seror, Jacques-Eric, Gottenberg, Eric, Hachulla, Veronique, Le Guern, Alain, Saraux, Jacques, Morel, Carine, Salliot, Anne, Tournadre, and Martin, Soubrier

Subjects
Fibromyalgia, Sjogren's Syndrome, Rheumatology, Physicians, Surveys and Questionnaires, Immunology, Humans, Immunology and Allergy
Abstract

Dryness, fatigue, and pain are classic symptoms in primary Sjögren's syndrome (pSS) but are also common in fibromyalgia (FM). We compared the characteristics of FM assessed by different criteria (American College of Rheumatology (ACR) 2016 and 1990 criteria), physician's opinion and Fibromyalgia Rapid Screening Tool (FiRST) questionnaire) in a cohort of patients with pSS.Eight hospital departments tested 134 patients with pSS according to AECG criteria from the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort.FM was present in 19%, 18%, 20%, and 29% of cases according to ACR 2016, ACR 1990 criteria, physician's opinion and the FiRST questionnaire, respectively. FM criteria-positive patients had higher EULAR SS Patient-Reported Index (ESSPRI) score, but not higher EULAR SS Disease Activity Index (ESSDAI) score. The objective measurements of dryness and the use of corticosteroids and immunosuppressive drugs did not differ between FM positive and negative patients. Regarding the ESSPRI dryness and fatigue subscale scores, depression and anxiety scores and the use of anxiolytics and antidepressants, the FiRST questionnaire exhibited a higher difference between positive and negative patients than ACR 2016 criteria. ACR 1990 and physician's opinion were somewhere in the middle. ACR 2016 exhibited moderate agreement with ACR 1990 (κ=0.52) and the physician's opinion (κ=0.60) and poor agreement with FiRST (κ=0.39).The FM criteria identified pSS patients with higher ESSPRI scores but not higher ESSDAI systemic disease scores. Agreement between the different FM criteria was moderate, and the characteristics they described did not fully coincide.

Published
2021

33. Évolution des prescriptions de biosimilaires d’étanercept et d’adalimumab en initiation dans la polyarthrite rhumatoïde en France : données du registre ART-SFR

Author

Adeline Ruyssen-Witrand, Yacine Boudali, Isabelle Pane, Alain Cantagrel, Pascale Thevenot, Martin Soubrier, Jacques Morel, Eric Houvenagel, Alain Saraux, André Basch, Marie-Elise Truchetet, Hubert Marotte, Emmanuelle Dernis, Pascal Claudepierre, René-Marc Flipo, Jacques-Eric Gottenberg, Philippe Ravaud, Xavier Mariette, and Raphaele Seror

Subjects
Rheumatology
Published
2022

34. 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

Author

George E Fragoulis, Elena Nikiphorou, Mrinalini Dey, Sizheng Steven Zhao, Delphine Sophie Courvoisier, Laurent Arnaud, Fabiola Atzeni, Georg MN Behrens, Johannes WJ Bijlsma, Peter Böhm, Costas A Constantinou, Silvia Garcia-Diaz, Meliha Crnkic Kapetanovic, Kim Lauper, Mariana Luís, Jacques Morel, György Nagy, Eva Polverino, Jef van Rompay, Marco Sebastiani, Anja Strangfeld, Annette de Thurah, James Galloway, and Kimme L Hyrich

Subjects
Antiviral Agents/therapeutic use, Adult, Immunology, Antirheumatic Agents/therapeutic use, Rheumatic Diseases/complications, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases, Rheumatology, Antirheumatic Agents, Tuberculosis, Humans, Immunosuppressive Agents/therapeutic use, Immunology and Allergy, Opportunistic Infections/diagnosis
Abstract

ObjectivesTo develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD).MethodsAn international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member.ResultsFour overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis againstPneumocystis jiroveciiseems to be beneficial in patients treated with daily doses >15–30 mg of prednisolone or equivalent for >2–4 weeks.ConclusionsThese recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

Published
2022

35. CXCR5/CXCL13 pathway, a key driver for migration of regulatory B10 cells, is defective in patients with rheumatoid arthritis

Author

J. Mielle, Pierre Corbeau, Kristina Schreiber, R. Audo, Laurence Macia, Jacques Morel, Claire Daien, Bernard Combe, Claire Rempenault, MORNET, Dominique, 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 de génétique humaine (IGH), The University of Sydney, 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), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Receptors, CXCR5, Chemokine, [SDV]Life Sciences [q-bio], Regulatory B cells, Cell, chemical and pharmacologic phenomena, Inflammation, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Synovial Fluid, medicine, Humans, Pharmacology (medical), Rheumatoid arthritis, CXCL13, Migration, B cell, 030304 developmental biology, B-Lymphocytes, Regulatory, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 0303 health sciences, biology, business.industry, Interleukine-10, Chemokine CXCL13, Interleukin-10, Interleukin 10, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, biology.protein, Cancer research, Chemokines, medicine.symptom, business, 030215 immunology, Homing (hematopoietic)
Abstract

Objectives Chemokines (CKs) are key players of immune-cell homing and differentiation. CK receptors (CKRs) can be used to define T-cell functional subsets. We aimed to characterize the CKR profile of the regulatory B-cell subset B10+ cells and investigate the CKs involved in their migration and differentiation in healthy donors and patients with RA. Methods RNA sequencing and cytometry were used to compare CKR expression between B10+ and B10neg cells. Migration of B10+ and B10neg cells and IL-10 secretion of B cells in response to recombinant CKs or synovial fluid (SF) were assessed. Results CXCR5 was expressed at a higher level on the B10+ cell surface as compared with other B cells (referred to as B10neg cells). In line with this, its ligand CXCL13 preferentially attracted B10+ cells over B10neg cells. Interestingly, synovial fluid from RA patients contained high levels of CXCL13 and induced strong and preferential migration of B10+ cells. Besides its role in attracting B10+ cells, CXCL13 also promoted IL-10 secretion by B cells. In RA patients, the level of CXCR5 on B-cell surface was reduced. The preferential migration of RA B10+ cells toward CXCL13-rich SF was lost and CXCL13 stimulation triggered less IL-10 secretion than in healthy donors. Conclusion Our results identify that the CXCR5/CXCL13 axis is essential for B10+ cell biology but is defective in RA. Restoring the preferential migration of B10+ within the affected joints to better control inflammation may be part of the therapeutic approach for RA.

Published
2021

36. One-month humoral response following two or three doses of messenger RNA coronavirus disease 2019 vaccines as primary vaccination in specific populations in France: first results from the Agence Nationale Recherche contre le Sida (ANRS)0001S COV-POPART cohort

Author

Paul Loubet, Linda Wittkop, Laetitia Ninove, Mathieu Chalouni, Benoit Barrou, Jean-Yves Blay, Maryvonne Hourmant, Eric Thouvenot, Martine Laville, Bruno Laviolle, Jean-Daniel Lelievre, Jacques Morel, Stéphanie Nguyen Quoc, Jean-Philippe Spano, Benjamin Terrier, Anne Thiebaut, Jean-Francois Viallard, François Vrtovsnik, Sophie Circosta, Laure Esterle, Axel Levier, Philippe Vanhems, Eric Tartour, Beatrice Parfait, Xavier de Lamballerie, and Odile Launay

Subjects
Microbiology (medical), Infectious Diseases, General Medicine
Abstract

We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults.Agence Nationale Recherche contre le Sida (ANRS)0001S-COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized.We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2-43.0], 57.4% [95% CI, 48.1-66.3] and 77.1% [95% CI, 65.6-86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9-65.2) (vs. 32.3% [95% CI, 16.7-51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9-85.7) (vs. 56.1% [95% CI, 46.2-65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies.A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies.

Published
2023

38. Hospitalization Risks for Neurological Disorders in Primary Sjögren’s Syndrome Patients

Author

Mura, Radjiv Goulabchand, Audrey Gabelle, Xavier Ayrignac, Nicolas Malafaye, Pierre Labauge, Danièle Noël, Jacques Morel, Camille Roubille, Lucie Barateau, Philippe Guilpain, and Thibault

Subjects
primary Sjögren’s syndrome, dementia, multiple sclerosis, encephalitis, peripheral neuropathy
Abstract

Primary Sjögren’s syndrome (pSS) can be associated with neurological and cognitive involvement, negatively affecting patients’ quality of life. The aim of this study was to assess whether pSS patients are at higher risk of hospitalization for neurological diseases. Through a nationwide retrospective study using the French Health insurance database (based on International Classification for Disease codes, ICD-10), we selected patients hospitalized with new-onset pSS between 2011 and 2018. We compared the incidence of hospitalization for dementia, multiple sclerosis (MS), encephalitis, and peripheral neuropathy with an age- and sex-matched (1:10) hospitalized control group. Adjusted Hazard Ratios (aHR) considered confounding factors, particularly socio-economic status and cardiovascular diseases. We analyzed 25,661 patients hospitalized for pSS, compared with 252,543 matched patients. The incidence of hospitalization for dementia was significantly higher in pSS patients (aHR = 1.27 (1.04–1.55); p = 0.018), as well as the incidence of hospitalization for MS, encephalitis, and inflammatory polyneuropathies (aHR = 3.66 (2.35–5.68), p < 0.001; aHR = 2.66 (1.22–5.80), p = 0.014; and aHR = 23.2 (12.2–44.5), p < 0.001, respectively). According to ICD-10 codes, pSS patients exhibited a higher incidence of hospitalization for dementia, encephalitis, MS, and peripheral neuropathies than controls. Physicians must be aware of these neurological risks to choose the most appropriate diagnostic work-up.

Published
2022
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39. Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjogren's syndrome

Author

Marie Wahren-Herlenius, Xavier Mariette, Jacques-Eric Gottenberg, Manuel Ramos-Casals, Chiara Baldini, Aike A. Kruize, Bei Xu, Virginia Fernandes Moça Trevisani, Gabriela Hernández-Molina, Jorge Sanchez-Guerrero, Pilar Brito-Zerón, Sung-Hwan Park, Sandra Gofinet Pasoto, Valeria Valim, Roberto Giacomelli, Roberta Priori, Kathy L. Sivils, Maureen Rischmueller, Wan-Fai Ng, Margit Zeher, Damien Sène, Berkan Armagan, Yasunori Suzuki, Valérie Devauchelle-Pensec, Marika Kvarnström, Soledad Retamozo, Guadalupe Fraile, Gunnel Nordmark, Sonja Praprotnik, Luca Quartuccio, Jacques Morel, Piotr Wiland, David A. Isenberg, Astrid Rasmussen, Seung-Ki Kwok, Stefano Bombardieri, Salvatore De Vita, Hendrika Bootsma, Benedikt Hofauer, Tamer A. Gheita, Thomas Mandl, Fabiola Atzeni, Xiaomei Li, Michele Bombardieri, Daniel Hammenfors, Antonina Minniti, Nihan Acar-Denizli, Roberto Gerli, Roser Solans, Levent Kilic, Eefje van der Heijden, Pulukool Sandhya, Hideki Nakamura, Raphaèle Seror, Debashish Danda, Ildikó Horváth, C. Vollenweider, Hospital Clinic (IDIBAPS), Mimar Sinan Üniversitesi, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], University of Debrecen [Hungary], Oklahoma Medical Research Foundation (OMRF), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, 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, Udine (DSMB), UO Complessa Reumatologia, 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], Division of Rheumatology, Seoul (Department of Internal Medicine), Unit of Experimental Rheumatology, Stockhom (Department of Medicine), University Medical Center, Hôpital 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, Vall d'Hebron University Hospital [Barcelona], The Queen Elizabeth Hospital, Adelaide, Department of Rheumatology, Skane University Hospital, Division of Rheumatology Kanazawa University Graduate School of Medicine, Kanazawa, Centre for Rheumatology - London, Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, Wroclaw Medical University, Uppsala University, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), University of Groningen [Groningen], Department of Immunology and Rheumatology, Nagasaki, Japan, 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), University of Freiburg [Freiburg], Queen Mary University London, Federal University of Sao Paulo (Unifesp), University of Bergen (UiB), Rheumatology Division, Hospital das Clinicas, Sao Paulo (HCFMUSP), Rheumatology Unit, Cordoba (Institute University of Biomedical Sciences University of Cordoba (IUCBC), Rheumatology Department, Cairo, Messina and Milan Univ, Milan, 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), Rheumatology, Buenos Aires, Department of Immunology [Debrecen, Hungary], Clinical Immunology & Rheumatology, Vellore, Department of Medical Area, University Hospital Santa Maria della Misericordia, Udine, Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Physics Department,Rome University 'LaSapienza' (Physics Department,Rome University 'LaSapienza'), 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, Rheumatology, Hacetttepe University Faculty of Medicine, Ankara, Laboratoire d'Immunologie [AP-HP Hôpital Kremlin-Bicêtre] (GHU Paris-Sud), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Translational Immunology Groningen (TRIGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Wrocław Medical University, 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), Universidad de Córdoba = University of Córdoba [Córdoba], Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), and Michel, Geneviève

Subjects
Male, Systemic disease, [SDV]Life Sciences [q-bio], Disease, primary Sjogren's syndrome, Severity of Illness Index, DISEASE, Cohort Studies, geoepidemiology, 0302 clinical medicine, Epidemiology, gender, Medicine, VASCULITIS, CRITERIA, Pharmacology (medical), Registries, African american, 0303 health sciences, Hispanic or Latino, ethnicity, phenotype, primary Sjögren's syndrome, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Sjogren's Syndrome, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Vasculitis, musculoskeletal diseases, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, education, primary Sjögren’s syndrome, DIAGNOSIS, White People, CLASSIFICATION, ethnicity, gender, geoepidemiology, phenotype, primary Sjögren’s syndrome, 03 medical and health sciences, Asian People, Rheumatology, Internal medicine, SCORE, Humans, COHORT, Rheumatology and Autoimmunity, 030304 developmental biology, 030203 arthritis & rheumatology, Reumatologi och inflammation, Information Dissemination, business.industry, MORTALITY, Racial Groups, GEOEPIDEMIOLOGY, AIR-POLLUTION, medicine.disease, Black or African American, Clinical research, Sjogren s, business
Abstract

Objective To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P Conclusion The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Published
2020

40. Rhumatologie, la multitude des options

Author

Jacques Morel, Denis Mulleman, Service de Rhumatologie [CHU de Montpellier], CHU Montpellier, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours

Subjects
Drug, medicine.medical_specialty, chronic inflammatory rheumatisms, medicine.drug_class, media_common.quotation_subject, rheumatology, MEDLINE, Disease, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, media_common, 030203 arthritis & rheumatology, biology, medicine.diagnostic_test, business.industry, General Medicine, Rheumatology, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Therapeutic drug monitoring, Immunology, biology.protein, biomarker, Biomarker (medicine), Antibody, business
Abstract

Le nombre d’anticorps (Ac) thérapeutiques disponibles en rhumatologie ne cesse de croître et concerne aussi bien les rhumatismes inflammatoires chroniques que les connectivites, les vascularites et, dans une moindre mesure, les pathologies osseuses et l’arthrose. Le choix d’un biomédicament repose aujourd’hui beaucoup sur les spécificités du médicament et des caractéristiques du patient. Il n’existe pas encore de véritables biomarqueurs prédictifs de réponse pour une médecine plus personnalisée. Le suivi sérique des Ac thérapeutiques et le dosage des anticorps anti-médicaments représentent un espoir pour adapter au mieux la posologie du médicament et décider d’un changement de traitement en fonction de l’activité de la maladie inflammatoire chronique.

Published
2019

41. Cancer incidence in primary Sjögren's syndrome: Data from the French hospitalization database

Author

Jacques Morel, Sylvain Lamure, Nicolas Malafaye, Thibault Mura, Nicolas Molinari, Pauline Rozier, William Jacot, Philine Witkowski Durand Viel, Philippe Guilpain, Danièle Noël, Cédric Lukas, Radjiv Goulabchand, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Montpelliérain Alexander Grothendieck (IMAG), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Retiveau, Nolwenn

Subjects
Oncology, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Epidemiology, Immunology, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Hospitalization, Lower risk, Hematological malignancies, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, MESH: Risk Factors, Internal medicine, Neoplasms, medicine, Immunology and Allergy, Humans, Solid neoplasms, MESH: Neoplasms, MESH: Incidence, education, Thyroid cancer, Retrospective Studies, education.field_of_study, MESH: Humans, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Cancer, Retrospective cohort study, MESH: Retrospective Studies, medicine.disease, Hospitalization, stomatognathic diseases, Sjogren's Syndrome, MESH: Sjogren's Syndrome, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Primary Sjögren's syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Cancer incidence
Abstract

International audience; The relationship between cancer and primary Sjögren's syndrome (pSS) is uncertain. While the increased risk of hematological malignancies is well-known, data on the comparative incidence of solid neoplasms is conflicting. This study aimed to explore the associations between cancer and pSS. This nationwide population-based retrospective study from the French health insurance database (PMSI) evaluated patients hospitalized with new-onset pSS from 2011 to 2018 against age- and sex-matched hospitalized controls (1:10). The incidence of hematological malignancies and solid neoplasms was compared between the two groups. Mortality and multiple cancer incidence were also evaluated. Adjusted Hazard Ratios (aHR) calculations included confounding factors, such as low socioeconomic status. Among 25,661 hospitalized patients with pSS versus 252,543 matched patients (median follow-up of 3.96 years), we observed a higher incidence rate of lymphomas (aHR, 1.97 [95% CI, 1.59-2.43]), Waldenström macroglobulinemia (aHR, 10.8 [6.5-18.0]), and leukemia (aHR, 1.61 [1.1-2.4]). Thyroid cancer incidence was higher (aHR, 1.7 [1.1-2.8]), whereas bladder and breast cancer incidences were lower (aHR, 0.58 [0.37-0.89] and 0.60 [0.49-0.74], respectively). pSS patients with breast cancer exhibited a lower mortality rate. A limitation was that the database only encompasses hospitalized patients, and immunological and histological details are not listed. We confirmed the increased risk of hematological malignancies and thyroid cancers among patients with pSS. The lower risk of breast cancer suggests a role of hormonal factors and raises questions of the concept of immune surveillance within breast tissue. Epidemiological and translational studies are required to elucidate the relationships between pSS and cancer.

Published
2021

42. En quoi la Covid-19 concerne la prise en charge des rhumatismes inflammatoires ? Place de la vaccination selon les cas

Author

Jacques Morel and Christophe Richez

Subjects
rhumatismes inflammatoires, Rheumatology, vaccins, arthritis, vaccines, Covid-19, Article
Abstract

La pandémie de Covid-19 a clairement impacté la prise en charge des rhumatismes inflammatoires chroniques (RIC) en termes de rupture de suivi et de rupture de traitement en raison du risque d’infection sévère liée à la maladie et aux traitements immuno-modulateurs. Des traitements permettent maintenant de prévenir ces formes sévères incluant des vaccins et des anticorps monoclonaux spécifiques dirigés contre la protéine « Spike » du virus SARS-CoV2. Parmi les traitements utilisés dans les RIC, les corticoïdes et le rituximab apparaissent clairement comme associés à une forme sévère de la Covid. La réponse humorale vaccinale après vaccination avec des vaccins à ARN messager (ARNm) apparaît diminuée sous méthotrexate, abatacept et surtout rituximab. Des schémas vaccinaux spécifiques ont déjà été proposés pour les patients sous rituximab et devraient s’affiner au fur et à mesure des connaissances car ces vaccins devraient s’inscrire maintenant dans le calendrier vaccinal de nos patients. Pour ceux qui ne développent pas d’anticorps après un schéma vaccinal complet, l’association d’anticorps casirivimab et imdévimab peut être administrée mensuellement en préventif ou en post-exposition.

Published
2021

44. Glutamine promotes the generation of B10

Author

Julie, Mielle, Jacques, Morel, Jamila, Elhmioui, Bernard, Combe, Laurence, Macia, Valérie, Dardalhon, Naomi, Taylor, Rachel, Audo, and Claire, Daien

Subjects
B-Lymphocytes, Regulatory, Glycogen Synthase Kinase 3, Glutamine, TOR Serine-Threonine Kinases, Interleukin-10
Abstract

Alterations in cell metabolism can shift the differentiation of immune cells toward a regulatory or inflammatory phenotype, thus, opening up new therapeutic opportunities for immune-related diseases. Indeed, growing knowledge on T- cell metabolism has revealed differences in the metabolic programs of suppressive Tregs as compared to inflammatory Th1 and Th17 cells. In addition to Tregs, IL-10-producing regulatory B cells are crucial for maintaining tolerance, inhibiting inflammation, and autoimmunity. Yet, the metabolic networks regulating diverse B-lymphocyte responses are not well known. Here, we show that glutaminase blockade decreased downstream mTOR activation and attenuated IL-10 secretion. Direct suppression of mTOR activity by rapamycin selectively impaired IL-10 production by B cells whereas secretion was restored upon Glycogen synthase kinase 3 (GSK3) inhibition. Mechanistically, we found mTORC1 activation leads to GSK3 inhibition, identifying a key signalling pathway regulating IL-10 secretion by B lymphocytes. Thus, our results identify glutaminolysis and the mTOR/GSK3 signalling axis, as critical regulators of the generation of IL-10 producing B cells with regulatory functions.

Published
2021

45. Risk of Cancer After Initiation of Targeted Therapies in Patients With Rheumatoid Arthritis and a Prior Cancer: Systematic Review With Meta-Analysis

Author

Cédric Lukas, Ronac Mamtani, Cécile Gaujoux-Viala, Jacques Morel, Thomas Barnetche, P. Szafors, Amélie Wetzman, and Bernard Combe

Subjects
Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Inflammatory arthritis, Cancer, medicine.disease, TNF inhibitor, Psoriatic arthritis, Rheumatology, Internal medicine, Rheumatoid arthritis, Meta-analysis, medicine, Rituximab, Skin cancer, business, medicine.drug
Abstract

Objective To determine the risk of recurrent or a new malignancy with exposure to targeted disease-modifying anti-rheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA), axial spondyloarthritis (AS), or psoriatic arthritis (PsA) and a history of cancer. Methods We performed a systematic search of the literature for articles published up to June 2019 that investigated adults with RA, AS or PsA who had a history of cancer and received biologic or targeted synthetic DMARDs (bDMARDs or tsDMARDs. We compared the risk of relapse or occurrence of new cancer between patients with and without bDMARDs. Rate ratios (RRs) with 95% confidence intervals (CIs) were estimated. The heterogeneity of the studies was evaluated by the Cochran Q test and the I² statistic. Results We included 24 observational studies of chronic inflammatory arthritis; 12 were included in the meta-analysis of RA patients receiving bDMARDs. As compared with RA patients with a history of cancer and not receiving bDMARDs, for those receiving any bDMARD, the overall RR for risk of neoplasia was 1.09 (95%CI [0.92-1.32], p=0.31, I²=8%); with tumor necrosis factor inhibitors, it was 1.11 (95%CI [0.85-1.46], p=0.45, I²=48%); and with rituximab, it was 0.79 (95%CI [0.41-1.53], p=0.49, I²=0%). The RR for risk of recurrence for skin cancer was 1.32 (95% CI [1.02-1.72], p=0.04, I²=0%) and for breast neoplasia 1.21 (95% CI [0.84-1.72], p=0.31, I²=0%). Conclusion Apart from skin cancers including melanoma, the risk of recurrent or new cancer is not increased with the initiation of bDMARDs for RA as compared with no bDMARDs.

Published
2021

46. A French cohort for assessing COVID-19 vaccine responses in specific populations

Author

Benoit Barrou, David-Axel Laplaud, Odile Launay, Stéphanie Nguyen, Jean-Daniel Lelièvre, Jean-Yves Blay, Benjamin Terrier, Martine Laville, Anne Thiebaut, Jacques Morel, Xavier de Lamballerie, Béatrice Parfait, Bruno Laviolle, Jean-François Viallard, Linda Wittkop, François Vrtovsnik, Jean-Philippe Spano, Paul Loubet, Maryvonne Hourmant, Marie Lachâtre, Eric Tartour, Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], 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), 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 Cochin [AP-HP], 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), Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Association Francaise d'Etudes et de Recherches sur l'Obesite, Partenaires INRAE, Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), 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 Universitaire [Grenoble] (CHU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS00001S, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Service d'Urologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-SU, Gestionnaire, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 de Paris (UP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], Université de Bordeaux (UB), Université de Paris (UP), Institut de Recherche pour le Développement (IRD), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Virulence Bactérienne et Infections Chroniques (VBIC), 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), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Grenoble, Université Paris Diderot - Paris 7 (UPD7), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- 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)-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), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Adolescent, Coronavirus disease 2019 (COVID-19), Epidemiology, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Immunocompromised Host, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Young adult, ComputingMilieux_MISCELLANEOUS, Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, business.industry, COVID-19, General Medicine, Middle Aged, Antibodies, Neutralizing, Virology, 3. Good health, Viral infection, 030220 oncology & carcinogenesis, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract

International audience; No abstract available

Published
2021

47. Practical Management of patients on anti-IL6R therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

Author

Jacques Morel, Anne Tournadre, Jérémie Sellam, Yoram Bouhnik, Divi Cornec, Valérie Devauchelle-Pensec, Philippe Dieudé, Philippe Goupille, Nicolas Kluger, Estibaliz Lazaro, Benoit Le Goff, Victor de Lédinghen, Thierry Lequerré, Gaëtane Nocturne, Raphaèle Seror, Marie-Elise Truchetet, Frank Verhoeven, Thao Pham, and Christophe Richez

Subjects
Arthritis, Rheumatoid, Inflammation, Rheumatology, Antirheumatic Agents, Humans
Published
2021

48. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Author

Anja, Strangfeld, Martin, Schäfer, Milena, A Gianfrancesco, Saskia, Lawson-Tovey, Jean, W Liew, Lotta, Ljung, Elsa, F Mateus, Christophe, Richez, Maria, J Santos, Gabriela, Schmajuk, Carlo, A Scirè, Emily, Sirotich, Jeffrey, A Sparks, Paul, Sufka, Thierry, Thomas, Laura, Trupin, Zachary, S Wallace, Sarah, Al-Adely, Javier, Bachiller-Corral, Suleman, Bhana, Patrice, Cacoub, Loreto, Carmona, Ruth, Costello, Wendy, Costello, Laure, Gossec, Rebecca, Grainger, Eric, Hachulla, Rebecca, Hasseli, Jonathan, S Hausmann, Kimme, L Hyrich, Zara, Izadi, Lindsay, Jacobsohn, Patricia, Katz, Lianne, Kearsley-Fleet, Philip, C Robinson, Jinoos, Yazdany, Pedro, M Machado, COVID-19 Global Rheumatology Alliance, COVID-19 Global Rheumatology Alliance Consortium Collaborators: COVID-19 Global Rheumatology Alliance Consortium, Brahim, Dahou, Marcelo, Pinheiro, Francinne, M Ribeiro, Anne-Marie, Chassin-Trubert, Sebastián, Ibáñez, Lingli, Dong, Lui, Cajas, Hesham, Hamoud, Jérôme, Avouac, Véronique, Belin, Raphaël, Borie, Pascal, Chazerain, Xavier, Chevalier, Pascal, Claudepierre, Gaëlle, Clavel, Marie-Eve, Colette-Cedoz, Bernard, Combe, Elodie, Constant, Nathalie, Costedoat-Chalumeau, Marie, Desmurs, Valérie, Devauchelle-Pensec, Mathilde, Devaux, Robin, Dhote, Yannick, Dieudonné, Fanny, Domont, Pierre-Marie, Duret, Mikaël, Ebbo, Esther, Ebstein, Soumaya El Mahou, Bruno, Fautrel, Renaud, Felten, René-Marc, Flipo, Violaine, Foltz, Antoine, Froissart, Joris, Galland, Véronique, Gaud-Listrat, Sophie, Georgin-Lavialle, Aude, Giraud-Morelet, Jeanine, S Giraudet-Le Quitrec, Philippe, Goupille, Sophie, Govindaraju-Audouard, Franck, Grados, Séverine, Guillaume-Czitrom, Marion, Hermet, Ambre, Hittinger-Roux, Christophe, Hudry, Isabelle, Kone-Paut, Sylvain La Batide Alanore, Pierre, Lafforgue, Sophie, Lahalle, Isabelle, Lambrecht, Vincent, Langlois, Jean-Paul, Larbre, Emmanuel, Ledoult, Christophe, Leroux, Frédéric, Liote, Alexandre TJ Maria, Hubert, Marotte, Arsène, Mekinian, Isabelle, Melki, Laurent, Messer, Catherine, Michel, Gauthier, Morel, Jacques, Morel, Marie-Noelle, Paris-Havard, Edouard, Pertuiset, Thao, Pham, Myriam, Renard, Sabine, Revuz, Sébastien, Rivière, Clémentine, Rousselin, Christian, Roux, Diane, Rouzaud, Jérémie, Sellam, Raphaele, Seror, Amelie, Servettaz, Vincent, Sobanski, Christelle, Sordet, Lionnel, Spielmann, Nathalie, Tieulié, Alice, Tison, Sophie, Trijau, Alexandre, Virone, Ursula, Warzocha, Daniel, Wendling, Frederik, N Albach, Peer, Aries, Elvira, Decker, Urs, Hartmann, Joerg, Henes, Bimba, F Hoyer, Andreas, Krause, Klaus, Krüger, Hanns-Martin, Lorenz, Ulf, Müller-Ladner, Alexander, Pfeil, Anne, Regierer, Jutta, G Richter, Markus, Rihl, Tim, Schmeiser, Hendrik, Schulze-Koops, Christof, Specker, Reinhard, E Voll, Stephanie, Werner, Gabriela MG Melgar, Mahdi, Vojdanian, Andreoli, Laura, Elena, Bartoloni-Bocci, Maurizio, Benucci, Francesco, Campanaro, Marta, Caprioli, Davide, Carboni, Greta, Carrara, Edoardo, Cipolletta, Chiara, Crotti, Gloria, Dallagiacoma, Paola, Faggioli, Rosario, Foti, Franceschini, Franco, Fredi, Micaela, Giacomo, Guidelli, Florenzo, Iannone, Gianpiero, Landolfi, Caludia, Lomater, Ceciclia, Nalli, Simone, Parisi, Luca, Quartuccio, Bernd, Raffeiner, Rossella, Reggia, Marta, Riva, Nicoletta, Romeo, Cinzia, Rotondo, Ettore, Silvagni, Luigi, Sinigaglia, Ilaria, Tinazzi, Anna, Zanetti, Giovanni, Zanframundo, Fatemah, Abutiban, Deshiré, Alpízar-Rodríguez, Marina, R Gabayet, Fedra, Irazoque, Xochitl, Jimenez, Eduardo, Martín, Angel AC Ortiz, Tatiana, S Rodriguez-Reyna, Diana, C Rosete, Erick AZ Tehozol, David, Vega, Beatriz, Zaueta, Nasra, Al-Adhoubi, Babur, Salim, Enrique, Giraldo, Ariel, Salinas, Manuel, Ugarte-Gil, Diogo, Almeida, Miguel, Bernardes, Rita, C Machado, Maria, Rato, Samar, Al-Emadi, Richard, Conway, Rachael, Flood, Juan, J Alegre-Sancho, Montserrat, C Coro, Natalia de la Torre-Rubio, Jose, C Esteban, Maria del Martin, Jose, G Puerta, Johan, Back, Maryam, Dastmalchi, Brigitte, Dupré, Emma, Grenholm, Aase, Hensvold, Ann, Knight, Servet, Akar, Ozan, C Icacan, Laura, Chadwick, Kirsty, Devine, Sasha, Dunt, Lucia, Fusi, Caroline, M Jones, Elizabeth, Macphie, Elena, Nikiphorou, Diana, O'Kane, Sheila, O'Reilly, Samir, Patel, Rosaria, Salerno, Lucy, Thornton, Jenny, Tyler, Claire, Vandevelde, Elizabeth, Warner, Su-Ann, Yeoh, Sara, Baig, Hammad, Bajwa, Byung, Ban, Vernon, Berglund, Cassandra, Calabrese, Kristin, D'Silva, Angela, Dahle, Kathryn, Dao, Nicole, Daver, William, Davis, Walter, Dorman, Ezzati, Fatemeh, Theodore, Fields, Jody, Hargrove, Melissa, Harvey, Maren, Hilton, Tiffany, Hsu, Arundathi, Jayatilleke, David, Karp, Gilbert, Kepecs, Neil, Kramer, Concetta, Lamore, Nicholas, Lebedoff, Susan, Leonard, Sushama, Mody, Jennifer, Morgan, Emily, Pfeifer, Guillermo, Quiceno, Robert, Quinet, Elliot, Rosenstein, Eric, Ruderman, Evangeline, Scopelitis, Naomi, Serling-Boyd, Faizah, Siddique, Archibald, Skemp, Jeffrey, Sparks, Derrick, Todd, Karen, T Toribio, Rachel, Wallwork, Tameka, Webb-Detiege, Douglas, White, Jeffrey, Wilson, Melanie, Winter, Leanna, Wise, Anne, Wolff, Kristen, Young, Jerald, Zakem, Joann, Zell, and Kurt Zimmerman, Leibniz Forschungsinstitut für Molekulare Pharmakolgie = Leibniz Institute for Molecular Pharmacology [Berlin, Allemagne] (FMP), Leibniz Association, University of California, University of Manchester [Manchester], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Umeå University, EULAR standing committee of People with Arthritis/Rheumatism in Europe (PARE), CHU Bordeaux [Bordeaux], Club Rhumatismes et Inflammation, Faculdade de Medicina [Lisboa], Universidade de Lisboa (ULISBOA), Università degli Studi di Ferrara (UniFE), McMaster University [Hamilton, Ontario], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Universidad de Alcalá - University of Alcalá (UAH), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Otago [Dunedin, Nouvelle-Zélande], Université de Lille, Technische Hochschule Mittelhessen - University of Applied Sciences [Giessen] (THM), University of Queensland [Brisbane], University College of London [London] (UCL), Repositório da Universidade de Lisboa, University of California (UC), Universidade de Lisboa = University of Lisbon (ULISBOA), Università degli Studi di Ferrara = University of Ferrara (UniFE), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Strangfeld, A, Schafer, M, Gianfrancesco, M, Lawson-Tovey, S, Liew, J, Ljung, L, Mateus, E, Richez, C, Santos, M, Schmajuk, G, Scire, C, Sirotich, E, Sparks, J, Sufka, P, Thomas, T, Trupin, L, Wallace, Z, Al-Adely, S, Bachiller-Corral, J, Bhana, S, Cacoub, P, Carmona, L, Costello, R, Costello, W, Gossec, L, Grainger, R, Hachulla, E, Hasseli, R, Hausmann, J, Hyrich, K, Izadi, Z, Jacobsohn, L, Katz, P, Kearsley-Fleet, L, Robinson, P, Yazdany, J, Machado, P, and HAL-SU, Gestionnaire

Subjects
Male, 0301 basic medicine, Aging, antirheumatic agents, Epidemiology, Azathioprine, Comorbidity, Disease, Global Health, Cardiovascular, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Odds Ratio, Immunology and Allergy, Registries, AcademicSubjects/MED00360, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, glucocorticoids, Middle Aged, health care, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Letter to the Editor (Other), 6.1 Pharmaceuticals, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Public Health and Health Services, Female, epidemiology, Rituximab, medicine.drug, medicine.medical_specialty, Clinical Sciences, Immunology, autoimmune disease, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Autoimmune Disease, General Biochemistry, Genetics and Molecular Biology, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, Rheumatology, Sulfasalazine, Rheumatic Diseases, Internal medicine, medicine, Humans, autoimmune diseases, outcome assessment, Aged, Rheumatology and Autoimmunity, 030203 arthritis & rheumatology, Reumatologi och inflammation, SARS-CoV-2, business.industry, Arthritis, Evaluation of treatments and therapeutic interventions, COVID-19, Odds ratio, medicine.disease, Arthritis & Rheumatology, Good Health and Well Being, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 Global Rheumatology Alliance, antirheumatic agent, glucocorticoid, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Published
2021

49. Practical management of patients on anti-IL17 therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

Author

Anne Tournadre, Jérémie Sellam, Jacques Morel, Denis Jullien, Yoram Bouhnik, Divi Cornec, Valérie Devauchelle-Pensec, Philippe Goupille, Nicolas Kluger, Estibaliz Lazaro, Benoit Le Goff, Victor de Lédinghen, Thierry Lequerré, Gaëtane Nocturne, Raphaèle Seror, Marie-Elise Truchetet, Frank Verhoeven, Christophe Richez, Thao Pham, Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [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), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de dermatologie [HCL Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Gastro-entérologie, CHU Hôpital Beaujon, Clichy, France, 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), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Dermatologie [Hôpital Bichat – Claude-Bernard - APHP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et maladies infectieuses, CHU de Bordeaux, F-33600, Pessac, Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Unité d'Hépatologie et transplantation hépatique, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Rhumatologie, Bicêtre, Le Kremlin-Bicêtre, France, Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Rhumatologie Bordeaux (SERVICE DE RHUMATOLOGIE), CHU Bordeaux [Bordeaux], and Service de Rhumatologie, Hôpital Sainte-Marguerite, Aix Marseille

Subjects
030203 arthritis & rheumatology, Arthritis, Rheumatoid, Inflammation, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Antirheumatic Agents, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract

International audience

Published
2021

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