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1. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study

Author: Silvio Danese, Jean-Frederic Colombel, Milan Lukas, Javier P Gisbert, Geert D'Haens, Bu'hussain Hayee, Remo Panaccione, Hyun-Soo Kim, Walter Reinisch, Helen Tyrrell, Young S Oh, Swati Tole, Akiko Chai, Kirsten Chamberlain-James, Meina Tao Tang, Stefan Schreiber, Nazimuddin Aboo, Tariq Ahmad, Xavier Aldeguer Mante, Matthieu Allez, Sven Almer, Romain Altwegg, Montserrat Andreu Garcia, Ramesh Arasaradnam, Sandro Ardizzone, Alessandro Armuzzi, Ian Arnott, Guy Aumais, Irit Avni-Biron, Peter Barrow, Ian Beales, Fernando Bermejo San Jose, Abraham Bezuidenhout, Livia Biancone, Michael Blaeker, Stuart Bloom, Bernd Bokemeyer, Fabrizio Bossa, Peter Bossuyt, Guillaume Bouguen, Yoram Bouhnik, Gerd Bouma, Raymond Bourdages, Arnaud Bourreille, Christian Boustiere, Tomas Brabec, Stephan Brand, Carsten Buening, Anthony Buisson, Guillaume Cadiot, Xavier Calvet Calvo, Franck Carbonnel, Daniel Carpio, Jae Hee Cheon, Naoki Chiba, Camelia Chioncel, Nicoleta-Claudia Cimpoeru, Martin Clodi, Gino Roberto Corazza, Rocco Cosintino, Jose Cotter, Thomas Creed, Fraser Cummings, Gian Luigi de' Angelis, Marc De Maeyer, Milind Desai, Etienne Desilets, Pierre Desreumaux, Olivier Dewit, Johanna Dinter, Ecaterina Daniela Dobru, Tomas Douda, Dan Lucian Dumitrascu, Matthias Ebert, Ana Echarri Piudo, Magdy Elkhashab, Chang Soo Eun, Brian Feagan, Roland Fejes, Catarina Fidalgo, Sigal Fishman, Bernard Flourié, Sharyle Fowler, Walter Fries, Csaba Fulop, Mathurin Fumery, Gyula G Kiss, Sonja Gassner, Daniel Gaya, Bastianello Germanà, Liliana Simona Gheorghe, Cyrielle Gilletta de Saint Joseph, Paolo Gionchetti, Adrian-Eugen Goldis, Raquel Gonçalves, Jean-Charles Grimaud, Tibor Gyökeres, Herve Hagege, Andrei Haidar, Heinz Hartmann, Peter Hasselblatt, Buhussain Hayee, Xavier Hebuterne, Per Hellström, Pieter Hindryckx, Helena Hlavova, Frank Hoentjen, Stefanie Howaldt, Ludek Hrdlicka, Kyu Chan Huh, Maria Isabel Iborra Colomino, Florentina Ionita-Radu, Peter Irving, Jørgen Jahnsen, ByungIk Jang, Jeroen Jansen, Seong Woo Jeon, Rodrigo Jover Martinez, Pascal Juillerat, Per Karlén, Arthur Kaser, Radan Keil, Deepak Kejariwal, Dan Keret, Reena Khanna, Dongwoo Kim, Duk Hwan Kim, Hyo-Jong Kim, Joo Sung Kim, Kueongok Kim, Kyung-Jo Kim, Sung Kook Kim, Young-Ho Kim, Jochen Klaus, Anna Kohn, Vladimir Kojecky, Ja Seol Koo, Robert Kozak, Milan Kremer, Tunde Kristof, Frederik Kruger, David Laharie, Adi Lahat-zok, Evgeny Landa, Jonghun Lee, Kang-Moon Lee, Kook Lae Lee, YooJin Lee, Frank Lenze, Wee Chian Lim, Jimmy Limdi, James Lindsay, Pilar Lopez Serrano, Edouard Louis, Stefan Lueth, Giovanni Maconi, Fazia Mana, Steven Mann, John Mansfield, Santino Marchi, Marco Marino, John Marshall, Maria Dolores Martin Arranz, Radu-Bogdan Mateescu, John McLaughlin, Simon McLaughlin, Ehud Melzer, Jessica Mertens, Paul Mitrut, Tamas Molnar, Vinciane Muls, Pushpakaran Munuswamy, Charles Murray, Timna Naftali, Visvakuren Naidoo, Yusuf Nanabhay, Lucian Negreanu, Augustin Nguyen, Thomas Ochsenkuehn, Ambrogio Orlando, Julian Panes Diaz, Maya Paritsky, Dong Il Park, Jihye Park, Luca Pastorelli, Markus Peck-Radosavljevic, Farhad Peerani, Javier Perez Gisbert, Laurent Peyrin-Biroulet, Laurence Picon, Marieke Pierik, Terry Ponich, Francisco Portela, Maartens Jeroen Prins, Istvan Racz, Khan Fareed Rahman, Jean-Marie Reimund, Max Reinshagen, Xavier Roblin, Rodolfo Rocca, Francesca Rogai, Gerhard Rogler, Agnes Salamon, Ennaliza Salazar, Zoltan Sallo, Sunil Samuel, Miquel de los Santos Sans Cuffi, Edoardo Vincenzo Savarino, Vincenzo Savarino, Guillaume Savoye, Andrada Seicean, Christian Selinger, David Martins Serra, Hang Hock Shim, SungJae Shin, Britta Siegmund, Jesse Siffledeen, Wayne Simmonds, Jan Smid, Jose Sollano, Geun Am Song, Alexander Speight, Ioan Sporea, Dirk Staessen, George Stancu, Alan Steel, David Stepek, Victor Stoica, Andreas Sturm, Gyorgy Szekely, Teck Kiang Tan, Carlos Taxonera Samso, John Thomson, Michal Tichy, Gabor Tamas Toth, Zsolt Tulassay, Marcello Vangeli, Marta Varga, Ana Vieira, Stephanie Viennot, Erica Villa, Petr Vitek, Harald Vogelsang, Petr Vyhnalek, Peter Wahab, Jens Walldorf, Byong Duk Ye, Christopher Ziady, Danese S., Colombel J.-F., Lukas M., Gisbert J.P., D'Haens G., Hayee B., Panaccione R., Kim H.-S., Reinisch W., Tyrrell H., Oh Y.S., Tole S., Chai A., Chamberlain-James K., Tang M.T., Schreiber S., Aboo N., Ahmad T., Aldeguer Mante X., Allez M., Almer S., Altwegg R., Andreu Garcia M., Arasaradnam R., Ardizzone S., Armuzzi A., Arnott I., Aumais G., Avni-Biron I., Barrow P., Beales I., Bermejo San Jose F., Bezuidenhout A., Biancone L., Blaeker M., Bloom S., Bokemeyer B., Bossa F., Bossuyt P., Bouguen G., Bouhnik Y., Bouma G., Bourdages R., Bourreille A., Boustiere C., Brabec T., Brand S., Buening C., Buisson A., Cadiot G., Calvet Calvo X., Carbonnel F., Carpio D., Cheon J.H., Chiba N., Chioncel C., Cimpoeru N.-C., Clodi M., Corazza G.R., Cosintino R., Cotter J., Creed T., Cummings F., de' Angelis G.L., De Maeyer M., Desai M., Desilets E., Desreumaux P., Dewit O., Dinter J., Dobru E.D., Douda T., Dumitrascu D.L., Ebert M., Echarri Piudo A., Elkhashab M., Eun C.S., Feagan B., Fejes R., Fidalgo C., Fishman S., Flourie B., Fowler S., Fries W., Fulop C., Fumery M., G Kiss G., Gassner S., Gaya D., Germana B., Gheorghe L.S., Gilletta de Saint Joseph C., Gionchetti P., Goldis A.-E., Goncalves R., Grimaud J.-C., Gyokeres T., Hagege H., Haidar A., Hartmann H., Hasselblatt P., Hebuterne X., Hellstrom P., Hindryckx P., Hlavova H., Hoentjen F., Howaldt S., Hrdlicka L., Huh K.C., Iborra Colomino M.I., Ionita-Radu F., Irving P., Jahnsen J., Jang B., Jansen J., Jeon S.W., Jover Martinez R., Juillerat P., Karlen P., Kaser A., Keil R., Kejariwal D., Keret D., Khanna R., Kim D., Kim D.H., Kim H.-J., Kim J.S., Kim K., Kim K.-J., Kim S.K., Kim Y.-H., Klaus J., Kohn A., Kojecky V., Koo J.S., Kozak R., Kremer M., Kristof T., Kruger F., Laharie D., Lahat-zok A., Landa E., Lee J., Lee K.-M., Lee K.L., Lee Y., Lenze F., Lim W.C., Limdi J., Lindsay J., Lopez Serrano P., Louis E., Lueth S., Maconi G., Mana F., Mann S., Mansfield J., Marchi S., Marino M., Marshall J., Martin Arranz M.D., Mateescu R.-B., McLaughlin J., McLaughlin S., Melzer E., Mertens J., Mitrut P., Molnar T., Muls V., Munuswamy P., Murray C., Naftali T., Naidoo V., Nanabhay Y., Negreanu L., Nguyen A., Ochsenkuehn T., Orlando A., Panes Diaz J., Paritsky M., Park D.I., Park J., Pastorelli L., Peck-Radosavljevic M., Peerani F., Perez Gisbert J., Peyrin-Biroulet L., Picon L., Pierik M., Ponich T., Portela F., Prins M.J., Racz I., Rahman K.F., Reimund J.-M., Reinshagen M., Roblin X., Rocca R., Rogai F., Rogler G., Salamon A., Salazar E., Sallo Z., Samuel S., Sans Cuffi M.D.L.S., Savarino E.V., Savarino V., Savoye G., Seicean A., Selinger C., Serra D.M., Shim H.H., Shin S., Siegmund B., Siffledeen J., Simmonds W., Smid J., Sollano J., Song G.A., Speight A., Sporea I., Staessen D., Stancu G., Steel A., Stepek D., Stoica V., Sturm A., Szekely G., Tan T.K., Taxonera Samso C., Thomson J., Tichy M., Toth G.T., Tulassay Z., Vangeli M., Varga M., Vieira A., Viennot S., Villa E., Vitek P., Vogelsang H., Vyhnalek P., Wahab P., Walldorf J., Ye B.D., and Ziady C.
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Population, Antibodies, Monoclonal, Humanized, Injections, Subcutaneou, Placebo, Severity of Illness Index, Gastroenterology, Young Adult, Double-Blind Method, Internal medicine, Gastrointestinal Agent, Clinical endpoint, medicine, education, Adverse effect, Aged, Aged, 80 and over, education.field_of_study, Hepatology, business.industry, Middle Aged, medicine.disease, Ulcerative colitis, Infliximab, Treatment Outcome, Etrolizumab, Concomitant, Colitis, Ulcerative, Female, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Human, medicine.drug
Abstract: Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.
Published: 2022
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2. Faster and less invasive tools to identify patients with ileal colonization by adherent‐invasive E. coli in Crohn's disease

Author: Clara Yzet, Anthony Buisson, Elisabeth Billard, Benjamin Pariente, Caroline Chevarin, Jérôme Filippi, Philippe Seksik, Nicolas Barnich, Laurent Peyrin-Biroulet, Gilles Bommelaer, Emilie Vazeille, Marion Goutte, Gilles Boschetti, Mathurin Fumery, Stéphane Nancey, Maria Nachury, Anaëlle Dubois, Bruno Pereira, Nathalie Ballet, Matthieu Allez, Stéphanie Rodriguez, Xavier Hébuterne, 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), CHU Amiens-Picardie, CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lesaffre, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], Hôpital Claude Huriez [Lille], INRAeUSC-2018Clermont Auvergne UniversityLesaffre InternationalMinistere de la Recherche et de la TechnologieI-SITE projectCAP 2025, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, Saliva, anti-E, Biopsy, adherent‐invasive E. coli, Gastroenterology, Inflammatory bowel disease, Feces, 0302 clinical medicine, Crohn Disease, Prospective Studies, Intestinal Mucosa, 0303 health sciences, Crohn's disease, biology, medicine.diagnostic_test, Colonoscopy, Antibodies, Bacterial, CEACAM6. IBD, medicine.anatomical_structure, Oncology, Biomarker (medicine), Female, Original Article, 030211 gastroenterology & hepatology, Antibody, adherent-invasive E, medicine.medical_specialty, IBD, Ileum, 03 medical and health sciences, inflammatory bowel disease, Internal medicine, Escherichia coli, medicine, anti‐E. coli antibodies, Humans, CEACAM6, 030304 developmental biology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, coli, coli antibodies, biology.protein, business, Biomarkers
Abstract: International audience; Background and AimsThe identification of Crohn's disease (CD)-associated adherent and invasive Escherichia coli (AIEC) is time-consuming and requires ileal biopsies. We aimed to identify a faster and less invasive methods to detect ileal colonization by AIEC in CD patients.MethodsCD patients requiring ileo-colonoscopy were consecutively enrolled in this prospective multicenter study. Samples from saliva, serum, stools, and ileal biopsies of CD patients were collected.ResultsAmong 102 CD patients, the prevalence of AIEC on ileal biopsies was 24.5%. The abundance and global invasive ability of ileal-associated total E. coli were respectively ten-fold (p = 0.0065) and two-fold (p = 0.0007) higher in AIEC-positive (vs. AIEC-negative), while abundance of total E. coli in the feces was not correlated with AIEC status in the ileum. The best threshold of ileal total E. coli was 60 cfu/biopsy to detect AIEC-positive patients, with high negative predictive value (NPV) (94.1%[80.3–99.3]), while the global invasive ability (>9000 internalized bacteria) was able to detect the presence of AIEC with high positive predictive value (80.0% [55.2–100.0]). Overall, 78.1% of the AIEC + patients were colonized by two or less different AIEC strains. The level of serum anti-total E. coli antibodies (AEcAb) was higher in AIEC-positive patients (p = 0.038) with a very high negative predictive value (96.6% [89.9–100.0]) (p = 0.038) for a cut-off value > 1.9 × 10−3.ConclusionsMore than two thirds of AIEC-positive CD patients were colonized by two or less AIEC strains. While stools samples are not accurate to screen AIEC status, the AEcAb level appears to be an attractive, rapid and easier biomarker to identify patients with Crohn's disease harboring AIEC.
Published: 2021
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3. Steroid-Free Deep Remission at One Year Does Not Prevent Crohn's Disease Progression: Long-Term Data From the TAILORIX Trial

Author: Filip Baert, David Laharie, Severine Vermeire, Christien J. van der Woude, Laurent Peyrin-Biroulet, Nicolas Duveau, Philippe Van Hootegem, Geert R. D'Haens, Edouard Louis, Laurence Picon, Cyrielle Gilletta, Guy Lambrecht, Matthieu Allez, Anthony Buisson, Jérôme Filippi, Maria Nachury, Peter Bossuyt, Yoram Bouhnik, Hedia Brixi, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology & Hepatology
Subjects: medicine.medical_specialty, Crohn's Disease, Disease, Deep Remission, Endoscopic Remission, Crohn Disease, Internal medicine, Clinical endpoint, Humans, Steroid free, Medicine, Prospective Studies, Crohn's disease, Hepatology, business.industry, Remission Induction, Gastroenterology, medicine.disease, Infliximab, Natural history, Treatment Outcome, Cohort, Disease Progression, Steroids, business, Follow-Up Studies, Abdominal surgery, medicine.drug
Abstract: Background & Aims: Crohn's disease (CD) patients included in the Tailored Treatment With Infliximab for Active Crohn's Disease (TAILORIX) trial started infliximab in combination with an immunosuppressant for 1 year. The aim of the present study was to determine the long-term disease course beyond the study period. Methods: We compared the outcomes of patients who did or did not reach the primary end point of the TAILORIX trial, defined as sustained corticosteroid-free clinical remission from weeks 22 through 54, with no ulcers on ileocolonoscopy at week 54. The primary outcome of this follow-up study was the progression-free survival of CD defined by anal or major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment. Results: The 95 patients (median disease duration, 4.5 mo; interquartile range, 1.0–56.6 mo) analyzed, including 45 (47%) who achieved the primary end point, were followed up for a median duration of 64.2 months (interquartile range, 57.6–69.9 mo) after the end of the study period. There was no significant difference in CD progression-free survival at 1, 3, and 5 years between patients who achieved the TAILORIX primary end point and patients who did not (P =.64). No difference was observed between both groups for each component of CD progression: anal surgery, major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment. Conclusions: Achieving a sustained clinical remission off steroids with complete endoscopic remission in this cohort of 95 patients with early CD was not associated with less disease progression. Prospective trials to define the therapeutic goals that change the natural history of CD and prevent complications are needed.
Published: 2022

4. Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study

Author: Mathurin Fumery, Jérôme Filippi, Vered Abitbol, Amélie Biron, David Laharie, Melanie Serrero, Romain Altwegg, Yoram Bouhnik, Laurent Peyrin‐Biroulet, Cyrielle Gilletta, Xavier Roblin, Guillaume Pineton de Chambrun, Lucine Vuitton, Anne Bourrier, Stephane Nancey, Jean‐Marc Gornet, Stephane Nahon, Guillaume Bouguen, Stephanie Viennot, Maria Nachury, Aurelien Amiot, Franck Brazier, Clara Yzet, Xavier Hebuterne, Guillaume Cadiot, Hedia Brixi, Pauline Rivière, Florian Poullenot, Xavier Treton, Carmen Stefanescu, Camille Zallot, Laurent Beaugerie, Philippe Seksik, Harry Sokol, Julien Kirchgesner, Gilles Boschetti, Bernard Flourié, Claire Gay, Pauline Danion, Chloe Venturin, Matthieu Allez, Clotilde Baudry, Benjamin Pariente, Pauline Wils, Charlotte Gagnière, Jenny Tannoury, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Bordeaux [Bordeaux], CHU Marseille, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Lille, CHI Créteil, GETAID, Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and 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)
Subjects: Adult, Male, medicine.medical_specialty, Pancolitis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Vedolizumab, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, Ustekinumab, Humans, Medicine, Pharmacology (medical), Adverse effect, Colectomy, Hepatology, business.industry, Remission Induction, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Ulcerative colitis, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Colitis, Ulcerative, 030211 gastroenterology & hepatology, medicine.symptom, business, medicine.drug, Cohort study
Abstract: International audience; Background Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. Aims To assess the real-world effectiveness and safety of ustekinumab in patients with UC. Methods From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score
Published: 2021
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5. S770 Health-Related Quality of Life With Ustekinumab vs Adalimumab for Induction and Maintenance Therapy in Biologic-Naïve Patients With Moderate-To-Severe Crohn’s Disease: IBDQ in the SEAVUE Study

Author: Matthieu Allez, Christopher Gasink, Silvio Danese, Bruce E. Sands, Peter M. Irving, Zhijie Ding, Erik Muser, Remo Panaccione, Tony Ma, Edward V. Loftus, James L. Izanec, Timothy Hoops, and James D. Lewis
Subjects: Moderate to severe, Health related quality of life, medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Gastroenterology, medicine.disease, Therapy naive, Maintenance therapy, Internal medicine, Ustekinumab, Adalimumab, medicine, business, medicine.drug
Published: 2021
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6. Long‐term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease

Author: Xavier Treton, Helene Corte, Jean-Marc Gornet, Jérôme Lambert, Nicolas Munoz-Bongrand, Mathias Vidon, Yves Panis, Jean-David Zeitoun, Philippe Seksik, Laurent Abramowitz, Matthieu Allez, and Léon Maggiori
Subjects: Adult, Anal fistula, medicine.medical_specialty, Combination therapy, Fistula, Population, Fibrin Tissue Adhesive, law.invention, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Randomized controlled trial, law, Humans, Rectal Fistula, Medicine, Cumulative incidence, education, Fibrin glue, Retrospective Studies, education.field_of_study, Crohn's disease, business.industry, Gastroenterology, medicine.disease, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Tissue Adhesives, 030211 gastroenterology & hepatology, business
Abstract: Aim The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short-term efficacy in a randomized controlled trial. No long-term data are available to assess the benefit of this treatment. Methods This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end-point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. Results In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti-tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow-up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end-point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. Conclusion An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease.
Published: 2020
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7. Long-term outcome of patients with acute severe ulcerative colitis responding to intravenous steroids

Author: Julien Kirchgesner, Antoine Meyer, Jean-Marc Gornet, Aurelien Amiot, Laurent Beaugerie, Matthieu Allez, Franck Carbonnel, and Robert Salameh
Subjects: medicine.medical_specialty, Multivariate analysis, Hepatology, business.industry, medicine.medical_treatment, Hazard ratio, Gastroenterology, Retrospective cohort study, medicine.disease, Ulcerative colitis, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, Medicine, 030211 gastroenterology & hepatology, Pharmacology (medical), 030212 general & internal medicine, business, Intravenous steroids, medicine.drug, Colectomy
Abstract: BACKGROUND The long-term outcome of patients with acute severe ulcerative colitis (ASUC) responding to intravenous steroids (IVS) has been poorly reported. AIMS To assess relapse-free survival in patients with ASUC responding to IVS. METHODS Between January 2006 and December 2017, 142 consecutive patients with ASUC (according to modified Truelove-and-Witts criteria) responding to IVS were included in this multicentre retrospective study. Relapse was defined by a partial Mayo Clinic score >4 and/or the need for another maintenance therapy. RESULTS Among the 142 included patients (100 naive of immunomodulator and/or biological agent) hospitalised for ASUC, 59 (41.5%) were treated at discharge with 5-aminosalicylic acid, 60 (42%) with immunomodulators, 18 (13%) with anti-tumour necrosis factor (TNF) agents and 5 (3.5%) with vedolizumab. After a median follow-up of 4.8 (2.6-7.3) years, 90 (63.4%) had relapsed and 12 (8.5%) had required colectomy. The probabilities of relapse-free survival were 58%, 48% and 40% at 1, 2 and 5 years respectively. The multivariate analysis demonstrated that patients with
Published: 2020
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8. Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study

Author: Vered Abitbol, Aurelien Amiot, Caroline Besson, Xavier Treton, Laurent Beaugerie, Catherine Thieblemont, Paul Coppo, Anouk Walter-Petrich, Thomas Aparicio, Georgia Malamut, Julien Kirchgesner, Lionel Galicier, Dominique Cazals-Hatem, Bénédicte Deau-Fischer, Matthieu Allez, Jean Marc Gornet, T. Severyns, Jérôme Lambert, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis, APHP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Hopital Saint-Louis [AP-HP] (AP-HP), CHU Henri Mondor AP-HP/UPEC, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Hôpital Beaujon, 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), Unité de neurophysiologie [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), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Male, medicine.medical_specialty, Lymphoma, [SDV]Life Sciences [q-bio], medicine.medical_treatment, IBD, Population, Antineoplastic Agents, Lymphoma, T-Cell, Inflammatory bowel disease, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Interquartile range, hemic and lymphatic diseases, Internal medicine, medicine, Humans, B-cell lymphoma, education, Digestive System Surgical Procedures, Neoplasm Staging, Biological Products, education.field_of_study, Chemotherapy, business.industry, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, medicine.disease, Hodgkin Disease, Chemotherapy regimen, 3. Good health, Intestines, 030220 oncology & carcinogenesis, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, France, Lymphoma, Large B-Cell, Diffuse, business, Immunosuppressive Agents
Abstract: Background and Aims The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. Methods A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. Results A total of 52 patients [male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%–94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%–100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. Conclusions In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.
Published: 2020
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9. Patients’ real-world experience with inflammatory bowel disease: A cross-sectional survey in tertiary care centres from the GETAID group

Author: Maria Nachury, Yoram Bouhnik, Melanie Serrero, Jerome Filippi, Xavier Roblin, Julien Kirchgesner, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered Abitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Matthieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Sara Tadbiri, Matthieu Allez, Stephanie Viennot, Arnaud Bourreille, David Laharie, Aurelien Amiot, Charlotte Gagniere, Jenny Tannoury, Benjamin Pariente, Pauline Wils, Carmen Stefanescu, Xavier Treton, Xavier Hébuterne, Nadia Arab, Virginie Cluzeau, Emilie Del Tedesco, Laurent Beaugerie, Philippe Seksik, Anne Bourrier, Cecilia Landmann, Harry Sokol, Laurent Siproudhis, Marie DeWitte, Catherine Reenaers, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Olivier DeWitt, Nicolas Mathieu, Sandie Pestour, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Nina Dib, Hedi Brixi, Guillaume Cadiot, Medina Boualit, Claire Painchart, Laurianne Plastaras, Romain Altwegg, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Stephane Nahon, Noemie Tavernier, Marion Simon, Baya Coulibaly, Morgane Amil, Duveau Nicolas, Sherine Khater, Mehdi Kaassis, Felix Goutorbe, Driffa Moussata, Laurence Picon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pasteur [Nice] (CHU), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service d'Hépatologie et de Gastroentérologie [Lyon], 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), 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 Hospitalier Universitaire de Toulouse (CHU Toulouse), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan), AbbVie, GETAID-patient experience study group: Aurelien Amiot , Sara Tadbiri , Charlotte Gagniere , Jenny Tannoury , Maria Nachury , Benjamin Pariente , Pauline Wils , Yoram Bouhnik , Carmen Stefanescu , Xavier Treton , Melanie Serrero , Jerome Filippi , Xavier Hébuterne , Nadia Arab , Virginie Cluzeau , Xavier Roblin , Emilie Del Tedesco , Laurent Beaugerie , Philippe Seksik , Anne Bourrier , Cecilia Landmann , Julien Kirchgesner , Harry Sokol , Guillaume Bouguen , Laurent Siproudhis , Marie DeWitte , Denis Franchimont , Guillaume Savoye , Anthony Buisson , Edouard Louis , Catherine Reenaers , Stephane Nancey , Gilles Boschetti , Claire Gay , Pauline Danion , Bernard Flourié , Vered Abitbol , Georgia Malamut , Jean-Marie Reimund , Benedicte Caron , Olivier DeWitt , Lucine Vuitton , Nicolas Mathieu , Sandie Pestour , Laurent Peyrin-Biroulet , Camille Zallot , Cyrielle Gilletta , Matthieu Allez , Jean-Marc Gornet , Clotilde Baudry , Stephanie Viennot , Arnaud Bourreille , Caroline Trang-Poisson , Nina Dib , Hedi Brixi , Guillaume Cadiot , Medina Boualit , Claire Painchart , Laurianne Plastaras , Romain Altwegg , Lucile Boivineau , Mathurin Fumery , Ludovic Caillo , David Laharie , Pauline Riviere , Florian Poullenot , Benoit Coffin , Henri Duboc , Stephane Nahon , Noemie Tavernier , Marion Simon , Baya Coulibaly , Morgane Amil , Duveau Nicolas , Sherine Khater , Mehdi Kaassis , Felix Goutorbe , Driffa Moussata , Laurence Picon, CHU Saint-Etienne, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-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), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Toulouse [Toulouse], CIC - Biotherapie - CHU 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), UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Crohn’s disease, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Cross-sectional study, [SDV]Life Sciences [q-bio], Disease, Patients experience, Inflammatory bowel disease, Tertiary care, digestive system, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Belgium, Physicians, Outpatients, medicine, Quantitative assessment, Humans, Adverse effect, Crohn's disease, Physician-Patient Relations, Hepatology, business.industry, Gastroenterology, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 3. Good health, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Family medicine, 030211 gastroenterology & hepatology, Female, France, Self Report, business
Abstract: International audience; BACKGROUND: Patients’ experience with healthcare professionals could influence their clinical outcomes. AIMS: To assess inflammatory bowel disease (IBD) patients’ experience with their disease, their treatment and their relationship with their physician. METHODS: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD. RESULTS: A quantitative assessment of the doctor-patient relationship revealed that patients’ knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample. CONCLUSION: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals.
Published: 2021
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10. Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial

Author: Laurent Peyrin-Biroulet, Ailsa Hart, Peter Bossuyt, Millie Long, Matthieu Allez, Pascal Juillerat, Alessandro Armuzzi, Edward V Loftus, Elham Ostad-Saffari, Astrid Scalori, Young S Oh, Swati Tole, Akiko Chai, Jennifer Pulley, Stuart Lacey, William J Sandborn, Humberto Aguilar, Tariq Ahmad, Evangelos Akriviadis, Xavier Aldeguer Mante, Istvan Altorjay, Ashwin Ananthakrishnan, Vibeke Andersen, Montserrat Andreu Garcia, Guy Aumais, Irit Avni-Biron, Jeffrey Axler, Kamran Ayub, Filip Baert, Mauro Bafutto, George Bamias, Isaac Bassan, Curtis Baum, Laurent Beaugerie, Brian Behm, Pradeep Bekal, Michael Bennett, Fernando Bermejo San Jose, Charles Bernstein, Dominik Bettenworth, Sudhir Bhaskar, Livia Biancone, Bahri Bilir, Michael Blaeker, Stuart Bloom, Verle Bohman, Francisco Javier Bosques Padilla, Yoram Bouhnik, Gerd Bouma, Raymond Bourdages, Stephan Brand, Brian Bressler, Markus Brückner, Carsten Buening, Franck Carbonnel, Thomas Caves, Jonathon Chapman, Jae Hee Cheon, Naoki Chiba, Camelia Chioncel, Dimitrios Christodoulou, Martin Clodi, Albert Cohen, Gino Roberto Corazza, Richard Corlin, Rocco Cosintino, Fraser Cummings, Robin Dalal, Silvio Danese, Marc De Maeyer, Carlos Fernando De Magalhães Francesconi, Aminda De Silva, Henry Debinski, Pierre Desreumaux, Olivier Dewit, Geert D'Haens, Sandra Di Felice Boratto, John Nik Ding, Tyler Dixon, Gerald Dryden, George Aaron Du Vall, Matthias Ebert, Ana Echarri Piudo, Robert Ehehalt, Magdy Elkhashab, Craig Ennis, Jason Etzel, Jan Fallingborg, Brian Feagan, Roland Fejes, Daniel Ferraz de Campos Mazo, Valéria Ferreira de Almeida Borges, Andreas Fischer, Alan Fixelle, Mark Fleisher, Sharyle Fowler, Bradley Freilich, Keith Friedenberg, Walter Fries, Csaba Fulop, Mathurin Fumery, Sergio Fuster, Gyula G Kiss, Santiago Garcia Lopez, Sonja Gassner, Kanwar Gill, Cyrielle Gilletta de Saint Joseph, Philip Ginsburg, Paolo Gionchetti, Eran Goldin, Adrian-Eugen Goldis, Hector Alejandro Gomez Jaramillo, Maciej Gonciarz, Glenn Gordon, Daniel Green, Jean-Charles Grimaud, Rogelio Guajardo Rodriguez, Zoltan Gurzo, Alexandra Gutierrez, Tibor Gyökeres, Ki Baik Hahm, Stephen Hanauer, John Hanson, William Harlan III, Peter Hasselblatt, Buhussain Hayee, Xavier Hebuterne, Peter Hendy, Melvin Heyman, Peter Higgins, Raouf Hilal, Pieter Hindryckx, Frank Hoentjen, Peter Hoffmann, Frank Holtkamp-Endemann, Gerald Holtmann, Gyula Horvat, Stefanie Howaldt, Samuel Huber, Ikechukwu Ibegbu, Maria Isabel Iborra Colomino, Peter Irving, Kim Isaacs, Kiran Jagarlamudi, Rajesh Jain, Sender Jankiel Miszputen, Jeroen Jansen, Jennifer Jones, John Karagiannis, Nicholas Karyotakis, Arthur Kaser, Lior Katz, Seymour Katz, Leo Katz, Nirmal Kaur, Edita Kazenaite, Reena Khanna, Sunil Khurana, Joo Sung Kim, Young-Ho Kim, Sung Kook Kim, Dongwoo Kim, Jochen Klaus, Dariusz Kleczkowski, Pavel Kohout, Bartosz Korczowski, Georgios Kouklakis, Ioannis Koutroubakis, Richard Krause, Tunde Kristof, Ian Kronborg, Annette Krummenerl, Limas Kupcinskas, Jorge Laborda Molteni, David Laharie, Adi Lahat-zok, Jonghun Lee, Kang-Moon Lee, Rupert Leong, Henry Levine, Jimmy Limdi, James Lindsay, Nilesh Lodhia, Edward Loftus, Randy Longman, Pilar Lopez Serrano, Edouard Louis, Maria Helena Louzada Pereira, John Lowe, Stefan Lueth, Milan Lukas, Giovanni Maconi, Finlay Macrae, Laszlo Madi-Szabo, Uma Mahadevan-Velayos, Everson Fernando Malluta, Fazia Mana, Peter Mannon, Gerasimos Mantzaris, Ignacio Marin Jimenez, Maria Dolores Martin Arranz, Radu-Bogdan Mateescu, Felipe Mazzoleni, Agnieszka Meder, Ehud Melzer, Jessica Mertens, Konstantinos Mimidis, Brent Mitchell, Tamas Molnar, Gregory Moore, Luis Alonso Morales Garza, Reme Mountifield, Vinciane Muls, Charles Murray, Bela Nagy, Markus Neurath, Augustin Nguyen, Remo Panaccione, William Pandak, Julian Panes Diaz, Jihye Park, Luca Pastorelli, Bhaktasharan Patel, Markus Peck-Radosavljevic, Gyula Pecsi, Farhad Peerani, Javier Perez Gisbert, Martin Pesta, Robert Petryka, Raymond Phillips, Marieke Pierik, Vijayalakshmi Pratha, Vlastimil Prochazka, Istvan Racz, Graham Radford-Smith, Daniel Ramos Castañeda, Odery Ramos Júnior, Jaroslaw Regula, Jean-Marie Reimund, Bryan Robbins, Xavier Roblin, Francesca Rogai, Gerhard Rogler, Jerzy Rozciecha, David Rubin, Azalia Yuriria Ruiz Flores, Maciej Rupinski, Grazyna Rydzewska, Sumona Saha, Simone Saibeni, Agnes Salamon, Zoltan Sallo, Bruce Salzberg, Douglas Samuel, Sunil Samuel, William Sandborn, Edoardo Vincenzo Savarino, Anja Schirbel, Robert Schnabel, Stefan Schreiber, John Scott, Shahriar Sedghi, Frank Seibold, Jakob Seidelin, Ursula Seidler, Ahmad Shaban, Ira Shafran, Aasim Sheikh, Alex Sherman, Haim Shirin, Patryk Smolinski, Geun Am Song, Konstantinos Soufleris, Alexander Speight, Dirk Staessen, Andreas Stallmach, Michael Staun, Daniel Stein, Hillary Steinhart, Jonathas Stifft, David Stokesberry, Andreas Sturm, Keith Sultan, Gyorgy Szekely, Kuldeep Tagore, Hugo Tanno, Lena Thin, Syed Thiwan, Carlton Thomas, Michal Tichy, Gabor Tamas Toth, Zsolt Tulassay, Jan Ulbrych, John Valentine, Marta Varga, Eduardo Vasconcellos, Byron Vaughn, Brenda Velasco, Francisco Velazquez, Severine Vermeire, Erica Villa, Aron Vincze, Harald Vogelsang, Miroslava Volfova, Lucine Vuitton, Petr Vyhnalek, Peter Wahab, Jens Walldorf, Mattitiahu Waterman, John Weber, L. Michael Weiss, Anna Wiechowska-Kozlowska, Elise Wiesner, Thomas Witthoeft, Robert Wohlman, Barbara Wozniak-Stolarska, Bruce Yacyshyn, Byong-Duk Ye, Ziad Younes, Lígia Yukie Sassaki, Cyrla Zaltman, Stefan Zeuzem, Neurosurgery, ANS - Neurovascular Disorders, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Peyrin-Biroulet L., Hart A., Bossuyt P., Long M., Allez M., Juillerat P., Armuzzi A., Loftus E.V., Ostad-Saffari E., Scalori A., Oh Y.S., Tole S., Chai A., Pulley J., Lacey S., Sandborn W.J., Aguilar H., Ahmad T., Akriviadis E., Aldeguer Mante X., Altorjay I., Ananthakrishnan A., Andersen V., Andreu Garcia M., Aumais G., Avni-Biron I., Axler J., Ayub K., Baert F., Bafutto M., Bamias G., Bassan I., Baum C., Beaugerie L., Behm B., Bekal P., Bennett M., Bermejo San Jose F., Bernstein C., Bettenworth D., Bhaskar S., Biancone L., Bilir B., Blaeker M., Bloom S., Bohman V., Bosques Padilla F.J., Bouhnik Y., Bouma G., Bourdages R., Brand S., Bressler B., Bruckner M., Buening C., Carbonnel F., Caves T., Chapman J., Cheon J.H., Chiba N., Chioncel C., Christodoulou D., Clodi M., Cohen A., Corazza G.R., Corlin R., Cosintino R., Cummings F., Dalal R., Danese S., De Maeyer M., De Magalhaes Francesconi C.F., De Silva A., Debinski H., Desreumaux P., Dewit O., D'Haens G., Di Felice Boratto S., Ding J.N., Dixon T., Dryden G., Du Vall G.A., Ebert M., Echarri Piudo A., Ehehalt R., Elkhashab M., Ennis C., Etzel J., Fallingborg J., Feagan B., Fejes R., Ferraz de Campos Mazo D., Ferreira de Almeida Borges V., Fischer A., Fixelle A., Fleisher M., Fowler S., Freilich B., Friedenberg K., Fries W., Fulop C., Fumery M., Fuster S., G Kiss G., Garcia Lopez S., Gassner S., Gill K., Gilletta de Saint Joseph C., Ginsburg P., Gionchetti P., Goldin E., Goldis A.-E., Gomez Jaramillo H.A., Gonciarz M., Gordon G., Green D., Grimaud J.-C., Guajardo Rodriguez R., Gurzo Z., Gutierrez A., Gyokeres T., Hahm K.B., Hanauer S., Hanson J., Harlan III W., Hasselblatt P., Hayee B., Hebuterne X., Hendy P., Heyman M., Higgins P., Hilal R., Hindryckx P., Hoentjen F., Hoffmann P., Holtkamp-Endemann F., Holtmann G., Horvat G., Howaldt S., Huber S., Ibegbu I., Iborra Colomino M.I., Irving P., Isaacs K., Jagarlamudi K., Jain R., Jankiel Miszputen S., Jansen J., Jones J., Karagiannis J., Karyotakis N., Kaser A., Katz L., Katz S., Kaur N., Kazenaite E., Khanna R., Khurana S., Kim J.S., Kim Y.-H., Kim S.K., Kim D., Klaus J., Kleczkowski D., Kohout P., Korczowski B., Kouklakis G., Koutroubakis I., Krause R., Kristof T., Kronborg I., Krummenerl A., Kupcinskas L., Laborda Molteni J., Laharie D., Lahat-zok A., Lee J., Lee K.-M., Leong R., Levine H., Limdi J., Lindsay J., Lodhia N., Loftus E., Longman R., Lopez Serrano P., Louis E., Louzada Pereira M.H., Lowe J., Lueth S., Lukas M., Maconi G., Macrae F., Madi-Szabo L., Mahadevan-Velayos U., Malluta E.F., Mana F., Mannon P., Mantzaris G., Marin Jimenez I., Martin Arranz M.D., Mateescu R.-B., Mazzoleni F., Meder A., Melzer E., Mertens J., Mimidis K., Mitchell B., Molnar T., Moore G., Morales Garza L.A., Mountifield R., Muls V., Murray C., Nagy B., Neurath M., Nguyen A., Panaccione R., Pandak W., Panes Diaz J., Park J., Pastorelli L., Patel B., Peck-Radosavljevic M., Pecsi G., Peerani F., Perez Gisbert J., Pesta M., Petryka R., Phillips R., Pierik M., Pratha V., Prochazka V., Racz I., Radford-Smith G., Ramos Castaneda D., Ramos Junior O., Regula J., Reimund J.-M., Robbins B., Roblin X., Rogai F., Rogler G., Rozciecha J., Rubin D., Ruiz Flores A.Y., Rupinski M., Rydzewska G., Saha S., Saibeni S., Salamon A., Sallo Z., Salzberg B., Samuel D., Samuel S., Sandborn W., Savarino E.V., Schirbel A., Schnabel R., Schreiber S., Scott J., Sedghi S., Seibold F., Seidelin J., Seidler U., Shaban A., Shafran I., Sheikh A., Sherman A., Shirin H., Smolinski P., Song G.A., Soufleris K., Speight A., Staessen D., Stallmach A., Staun M., Stein D., Steinhart H., Stifft J., Stokesberry D., Sturm A., Sultan K., Szekely G., Tagore K., Tanno H., Thin L., Thiwan S., Thomas C., Tichy M., Toth G.T., Tulassay Z., Ulbrych J., Valentine J., Varga M., Vasconcellos E., Vaughn B., Velasco B., Velazquez F., Vermeire S., Villa E., Vincze A., Vogelsang H., Volfova M., Vuitton L., Vyhnalek P., Wahab P., Walldorf J., Waterman M., Weber J., Weiss L.M., Wiechowska-Kozlowska A., Wiesner E., Witthoeft T., Wohlman R., Wozniak-Stolarska B., Yacyshyn B., Ye B.-D., Younes Z., Yukie Sassaki L., Zaltman C., and Zeuzem S.
Subjects: Adult, Male, Ulcerative Colitis Flare, medicine.medical_specialty, Asia, Adolescent, Oceania, Population, Antibodies, Monoclonal, Humanized, Injections, Subcutaneou, Placebo, Severity of Illness Index, law.invention, Middle East, Young Adult, Maintenance therapy, Randomized controlled trial, law, Internal medicine, Gastrointestinal Agent, medicine, Adverse effect, education, Aged, Aged, 80 and over, Tumor Necrosis Factor Inhibitor, education.field_of_study, Hepatology, business.industry, Remission Induction, Gastroenterology, Middle Aged, South America, medicine.disease, Ulcerative colitis, Europe, Treatment Outcome, Etrolizumab, North America, Colitis, Ulcerative, Female, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Human
Abstract: Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.
Published: 2022

11. Mitochondrial impairment drives intestinal stem cell transition into dysfunctional Paneth cells predicting Crohn’s disease recurrence

Author: Matthieu Allez, Elisabeth Gleisinger, Nadine Waldschmitt, Andreas Blutke, Nassim Hammoudi, Dirk Haller, Sevana Khaloian, Emanuel Berger, Eva Rath, Amira Metwaly, and Pieter Giesbertz
Subjects: Inflammatory Bowel Disease, intestinal stem cell, Gastroenterology, LGR5, Inflammation, Mitochondrion, Biology, medicine.disease, digestive system, Intestinal epithelium, Inflammatory bowel disease, ddc, Crohn's disease, medicine.anatomical_structure, energy metabolism, Paneth cell, medicine, Cancer research, intestinal epithelium, Ileitis, Stem cell, medicine.symptom
Abstract: ObjectiveReduced Paneth cell (PC) numbers are observed in inflammatory bowel diseases and impaired PC function contributes to the ileal pathogenesis of Crohn’s disease (CD). PCs reside in proximity to Lgr5+ intestinal stem cells (ISC) and mitochondria are critical for ISC-renewal and differentiation. Here, we characterise ISC and PC appearance under inflammatory conditions and describe the role of mitochondrial function for ISC niche-maintenance.DesignIleal tissue samples from patients with CD, mouse models for mitochondrial dysfunction (Hsp60Δ/ΔISC) and CD-like ileitis (TNFΔARE), and intestinal organoids were used to characterise PCs and ISCs in relation to mitochondrial function.ResultsIn patients with CD and TNFΔARE mice, inflammation correlated with reduced numbers of Lysozyme-positive granules in PCs and decreased Lgr5 expression in crypt regions. Disease-associated changes in PC and ISC appearance persisted in non-inflamed tissue regions of patients with CD and predicted the risk of disease recurrence after surgical resection. ISC-specific deletion of Hsp60 and inhibition of mitochondrial respiration linked mitochondrial function to the aberrant PC phenotype. Consistent with reduced stemness in vivo, crypts from inflamed TNFΔARE mice fail to grow into organoids ex vivo. Dichloroacetate-mediated inhibition of glycolysis, forcing cells to shift to mitochondrial respiration, improved ISC niche function and rescued the ability of TNFΔARE mice-derived crypts to form organoids.ConclusionWe provide evidence that inflammation-associated mitochondrial dysfunction in the intestinal epithelium triggers a metabolic imbalance, causing reduced stemness and acquisition of a dysfunctional PC phenotype. Blocking glycolysis might be a novel drug target to antagonise PC dysfunction in the pathogenesis of CD.
Published: 2020
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12. Infliximab Exposure Associates With Radiologic Evidence of Healing in Patients With Crohn’s Disease

Author: Severine Vermeire, Valérie Laurent, Anthony Buisson, Guy Lambrecht, Edouard Louis, Céline Savoye-Collet, Hedia Brixi, Sylvie Chevret, Laurent Peyrin-Biroulet, Filip Baert, Marieke Pierik, Jordi Rimola, Matthieu Allez, Philippe Van Hootegem, Philip Caenepeel, Alexandre Aubourg, Jérôme Filippi, Benjamin Pariente, Magaly Zappa, Jacques Moreau, Peter Bossuyt, Geert R. D'Haens, Yoram Bouhnik, Janneke van der Woude, David Laharie, Martine De Vos, Ragna Vanslembrouck, Yves De Bruecker, Sofie Devuysere, Denis Franchimont, Fazia Mana, Bas Oldenburg, Erwin Dreesen, Service d'imagerie médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Adult, Male, musculoskeletal diseases, medicine.medical_specialty, TAILORIX, [SDV]Life Sciences [q-bio], education, Anti-TNF Agent, anti-TNF agent, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Gastrointestinal Agents, Interquartile range, response to therapy, Internal medicine, medicine, Humans, Prospective Studies, prognostic factor, Response to Therapy, Crohn's disease, Hepatology, Receiver operating characteristic, business.industry, Prognostic Factor, Area under the curve, Biomarker, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Infliximab, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Pharmacodynamics, Biomarker (medicine), Trough level, biomarker, 030211 gastroenterology & hepatology, Female, business, medicine.drug
Abstract: BACKGROUND & AIMS: Higher infliximab trough levels are associated with clinical and endoscopic remission in patients with Crohn's disease (CD). We investigated pharmacodynamic features of infliximab and radiological healing. METHODS: We performed a substudy of the TAILORIX trial (patients with active luminal CD in Europe, treated with infliximab), analyzing baseline and week 54 magnetic resonance enterography (MRE) data. MREs were scored using the MaRIA score by blinded central readers. Radiologic response and remission were defined, based on MaRIA criteria in all segments, as scores below 11 and 7, respectively. We collected data on infliximab trough levels, biomarkers, and endoscopic findings. Our primary aim was to evaluate pharmacodynamic features associated with radiologic response and remission, based on MRE assessments at baseline and at 54 weeks after initiation of infliximab therapy. RESULTS: We analyzed data from 36 patients (50% female; median age 35.7 years; interquartile age range, 25.6-48.6 years; median disease duration, 1.5 months; interquartile duration range, 0.6-22.4 months). At week 54 of treatment, 36.4% of patients had a radiologic response, 30.3% of patients were in remission, and 71% had endoscopic features of remission. At baseline, there was a correlation between the CD endoscopic index of severity and MaRIA scores (κ = 0.46; P = .008), but we found no correlation at week 54 (κ = 0.06; P = .75). Radiologic remission correlated with infliximab trough level at week 14 (P = .049) when the infliximab trough level cut-off value was set at 7.8 μg/mL (area under the curve, 0.74; 75% sensitivity; 86% specificity; 90% negative predictive value; 57% positive predictive value). Radiologic response correlated with infliximab trough levels at week 14 (P = .048) when the infliximab trough level cut-off value was set at 7.8 μg/mL (area under the curve, 0.73; 70% sensitivity; 90% specificity; 86% negative predictive value; 78% positive predictive value) and with continuous pharmacologic evidence of response (infliximab trough levels above 5.0 μg/mL at all time points) (P = .034). CONCLUSIONS: In a substudy of data from the TAILORIX trial of patients with active luminal CD, we identified a relationship between exposure to infliximab and radiologic evidence of outcomes. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:19 issue:5 pages:947-+ ispartof: location:United States status: published
Published: 2021
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13. Chronic pouchitis and Crohn's disease of the pouch after ileal pouch-anal anastomosis: Incidence and risk factors

Author: Franck Carbonnel, Yves Panis, Aurelien Amiot, Clément Bresteau, A. Brouquet, Nicola de’Angelis, Julien Kirchgesner, Antoine Meyer, Jérémie H. Lefevre, Matthieu Allez, Laurent Beaugerie, and Yoram Bouhnik
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Pouchitis, Gastroenterology, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Risk Factors, Internal medicine, medicine, Humans, Cumulative incidence, Retrospective Studies, Crohn's disease, Hepatology, Proctocolectomy, business.industry, Incidence (epidemiology), Incidence, Proctocolectomy, Restorative, Middle Aged, medicine.disease, Ulcerative colitis, 030220 oncology & carcinogenesis, Disease Progression, 030211 gastroenterology & hepatology, Female, Pouch, business
Abstract: Background Restorative proctocolectomy with ileal-pouch anal-anastomosis (IPAA) is the operation of choice for patients with ulcerative colitis (UC) or with inflammatory bowel diseases unclassified (IBDU). Aims to assess the incidence and risk factors of chronic pouchitis (CP) and Crohn's disease of the pouch (CDP) in patients with UC or IBDU. Methods We conducted a retrospective study. We included consecutive patients who underwent IPAA between 2011 and 2019. The main outcome was the occurrence of CP or CDP. We looked for risk factors with multivariable and a least absolute shrinkage and selection operator (LASSO) Cox models. Results 247 patients were included. The 5-year cumulative incidence of CP or CDP was 35.3% (95%CI: 26.2–43.2). In multivariable analysis, diagnosis of IBDU, age less than 35 years at surgery and extra-intestinal manifestations other than articular and primary sclerosing cholangitis were associated with higher incidence. The LASSO analysis identified these three prognostic factors and articular manifestations. In patients with two or more prognostic factors, 5-year cumulative incidence, was 65.2% (95%CI: 41.8–79.2). Conclusions Five years after IPAA, approximately one-third of patients had either CP or CDP. Risk factors were IBDU, an age less than 35 years at surgery, articular manifestations and other extra-intestinal manifestations.
Published: 2021

14. Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

Author: Arnaud Bourreille, Julien Branche, Laurent Beaugerie, Yoram Bouhnik, Stéphane Nahon, Mathurin Fumery, Benoit Coffin, Philippe Marteau, Matthieu Allez, Guillaume Savoye, Javier P. Gisbert, Martine De Vos, Jean-Yves Mary, Jacques Moreau, Elena Ricart, Laurent Peyrin-Biroulet, Xavier Roblin, Jérôme Filippi, Franck Carbonnel, Maria Esteve, Olivier Dewit, Aurelien Amiot, David Laharie, Martti Färkkilä, Lucine Vuitton, Anthony Buisson, Antonio López-Sanromán, Gert Van Assche, Frank Zerbib, CHU Bordeaux [Bordeaux], CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Hôtel-Dieu de Nantes, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Hôpital Beaujon [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital l'Archet, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital JeanMinjoz, CHU Toulouse [Toulouse], Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Université Catholique de Louvain = Catholic University of Louvain (UCL), Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), CHU Amiens-Picardie, 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, Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), 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), Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital Louis Mourier - AP-HP [Colombes], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Nord (Saint Etienne), University Hospitals Leuven [Leuven], University of Helsinki, CHU Tenon [AP-HP], Sorbonne Université (SU), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Ghent University Hospital, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Department of Medicine, Gastroenterologian yksikkö, Helsinki University Hospital Area, Hôpital Archet 2 [Nice] (CHU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service de Gastro-Entérologie [CHRU Besançon], Service de Gastro-entérologie et Nutrition[Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Hospital Clínic de Barcelona, Cliniques Universitaires Saint-Luc [Bruxelles], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'Hépato-gastroentérologie [CHU Saint-Etienne], Hospital Universitario Mutua de Terrassa, Helsinki University Central Hospital [Finland] (HUCH), Universidad Autonoma de Madrid (UAM), Hospital Universitario de la Princesa, Service d'Hépato-gastro-entérologie [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastro-entérologie [CHRU Nancy], Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Association Francois Aupetit, CHU Rouen, Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DESSAIVRE, Louise, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, MAINTENANCE THERAPY, UCEIS, [SDV]Life Sciences [q-bio], Gastroenterology, Severity of Illness Index, Mucosal Healing, law.invention, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Randomized controlled trial, law, Interquartile range, VEDOLIZUMAB, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, INDEX, OUTCOMES, Hepatology, business.industry, ulcerative Colitis, INDUCTION, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, REMISSION, medicine.disease, Ulcerative colitis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Infliximab, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, 3121 General medicine, internal medicine and other clinical medicine, Cyclosporine, 030211 gastroenterology & hepatology, Colitis, Ulcerative, Steroids, business, Steroid refractory, medicine.drug
Abstract: International audience; BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p
Published: 2021
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15. Challenges and Opportunities in IBD Clinical Trial Design

Author: Marla C. Dubinsky, Rory Collins, Maria T. Abreu, Vipul Jairath, James D. Lewis, James Lindsay, Miriam Merad, Siew Ng, Remo Panaccione, Julian Panes, Bruce Sands, Corey A. Siegal, Siddarth Singh, Severine Vermeire, Vineet Ahuja, Matthieu Allez, Ashwin Ananthakrishnan, Willem Bemelman, Jonathan Braun, Jean-Frederic Colombel, Silvio Danese, Geert D’Haens, André D’Hoore, Axel Dignass, Iris Dotan, Miguel Angel Gassul, Anne Griffiths, Jonas Halfvarson, Stephen Hanauer, Paulo Kotze, Ioannis Koutroubakis, Edward Loftus, Edouard Louis, Fernando Magro, Gerassimos Mantzaris, Jean-Yves Mary, Dermot McGovern, Pia Munkholm, Colm O’Morain, Yves Panis, Laurent Peyrin-Biroulet, Cosimo Prantera, Zhihua Ran, Britta Siegmund, Mark Silverberg, Eduard Stange, Stephan Targan, Curt Tysk, Simon Travis, Morton Vatn, Yesus Yamamoto-Furusho, Janske Aarts, Brihad Abhyankar, Harris Ahmad, Richard Aranda, Vipin Arora, Jalil Benjacoub, Sofie Berg, Robin Besuyen, Daniela Bojic, Valerio Carriero, Fabio Cataldi, Laurence D’Agay, Silvia Delgado-Aros, Paul Giannasca, Kavitha Goyal, Roland Greinwald, Savion Gropper, Shunsuke Kageyama, Raphaël Laoun, Barrett Levesque, Trevor Lissoos, Irene Modesto, Ralf Mohrbacher, Ralph Mueller, April Naegeli, Snehal Naik, Deanne Nguyen, Wojciech Niezychowski, Caitriona O’Brien, Irina Odnoletkova, Alessandra Oortwijn, Kun K.T. Park, Waldemar Radziszewski, Leonardo Salese, Johannes Spleiss, Andrea Stancati, Amanda Tatro, Jennifer Thompson, Robert Hofmann, Javier Zambrano, Wen Zhou, Ellen Zigmont, Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology and Hepatology
Subjects: medicine.medical_specialty, Ibd clinical, Crohn's disease, Hepatology, business.industry, Inflammatory Bowel Disease, Gastroenterology, Crohn's Disease, medicine.disease, Ulcerative colitis, Crohn's Disease Activity Index, Inflammatory bowel disease, law.invention, Food and drug administration, Clinical trial, Randomized controlled trial, law, Internal medicine, medicine, Ulcerative Colitis, Clinical Trials, business
Published: 2021
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16. Indications de l’autogreffe de cellules hématopoïétiques dans la Maladie de Crohn : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire

Author: Ibrahim Yakoub-Agha, Zora Marjanovic, Manuela Badoglio, David Laharie, Montserrat Rovira, Xavier Treton, M. Puyade, Miguel Torregrosa Díaz Jose, Dominique Farge, Laurent Alric, Ginette Fotsing, Grégory Pugnet, Cristina Castilla Llorente, Louis Terriou, Matthieu Allez, My-Linh Tran-Minh, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Hospital Clínic de Barcelona [Catalonia, Spain], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Purpan [Toulouse], CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), CCSD, Accord Elsevier, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département d'hématologie [Gustave Roussy], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Oncology, Mobilisation des de cellules hématopoïétiques, Cancer Research, medicine.medical_specialty, Conditionnement, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Disease, Monoclonal antibody, Post autologous stem cell transplantation follow-up, Suivi post autogreffe, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Soins de support, Autologous hematopoietic cell transplantation, Internal medicine, Medicine, Radiology, Nuclear Medicine and imaging, Crohn's disease, Autogreffe de cellules hématopoïétiques, business.industry, Conditionning regimen, Hematopoietic stem cell, Hematology, General Medicine, Stem-cell therapy, medicine.disease, Supportive Care, Maladie de Crohn, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mobilization of hematopoietic cell, Immunosuppression intensive, Methotrexate, Intensive Immunosuppression, business, medicine.drug
Abstract: International audience; Crohn's Disease (CD) is an auto-inflammatory disease, which may involve the entire gastro-intestinal tract. CD is diagnosed on several clinical, biological, endoscopic and histological criteria. First line therapy is based on oral or iv steroids. In case of steroids dependence or resistance, several types of immunosuppressive or immunomodulating therapies are available: classical antimetabolites (thiopurines or methotrexate) or monoclonal antibodies against TNFα, against interleukin 12/23 or against integrin. Nonetheless, Crohn's disease may remain active despite the use of several lines of therapy. In such cases, autologous hematopoietic cell transplantation (AHCT) is an effective therapeutic option in highly selected CD patients with specific criteria. The MATHEC-SFGM-TC Good Clinical Practice Guidelines (GCPG) were developed by a multidisciplinary group of experts including gastroenterologists, hematologists and members of the reference center for stem cell therapy in auto-immune diseases (MATHEC), including members of the French groupe d'étude thérapeutique des affections inflammatoires du tube digestif(GETAID) under the auspices of the French speaking Society of bone marrow transplantation and cellular therapy (SFGM-TC). The aim of the present guidelines is to define the eligibility criteria for CD patients when candidates to AHCT, the procedures for mobilization of hematopoietic stem cell (HSC), conditioning regimen and standardized follow-up after AHCT including monitoring of gastroenterological treatments during AHCT and thereafter throughout all follow-up.
Published: 2020
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17. Safety of Hydrocortisone Premedication Discontinuation in Patients with Inflammatory Bowel Disease on Maintenance Therapy with Infliximab: a Prospective Clinical and Pharmacological Study

Author: Pascal Houzé, Clotilde Baudry, Deborah Hassid, Marion Simon, Matthieu Allez, Marianne Maillet, Justine Vivier-Chicoteau, Nassim Hammoudi, My-Linh Tran-Minh, Jean-Marc Gornet, and Paul McLellan
Subjects: Adult, Male, medicine.medical_specialty, Combination therapy, Hydrocortisone, Premedication, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Gastrointestinal Agents, Internal medicine, medicine, Humans, Prospective Studies, 030203 arthritis & rheumatology, business.industry, Gastroenterology, General Medicine, medicine.disease, Inflammatory Bowel Diseases, Infliximab, Discontinuation, Cohort, 030211 gastroenterology & hepatology, Female, business, medicine.drug
Abstract: Background Hydrocortisone premedication reduces the risk of antibodies to infliximab [ATIs] formation in patients receiving infliximab [IFX] therapy for inflammatory bowel disease [IBD]. Aim We aimed to determine the safety of hydrocortisone premedication withdrawal in IBD patients with sustained clinical response on maintenance therapy with IFX. Methods We performed an observational prospective pharmacoclinical study in a tertiary referral centre, including all consecutive IBD outpatients with no previous IFX infusion reaction and in clinical remission on maintenance IFX [alone or in combination therapy] for at least 6 months. This cohort was followed for 1 year after discontinuation of hydrocortisone premedication. Results Among the 268 IBD outpatients, 95 patients met the inclusion criteria [mean age 38 years; 64% male; 80% Crohn’s disease; 45% combination therapy]. The median IFX duration was 5 years [0.54–14] with a mean infused dose of 533 mg [200–1000] and a mean interval duration of 7.9 weeks [4–10]. None of the patients developed permanent ATIs or infusion-related reaction at 1 year. Four patients developed transient ATIs without loss of clinical response. There was no significant variation of infliximab serum trough levels [5.5 µg/mL vs 5.9 µg/mL] measured at the time of the three IFX infusions before and after hydrocortisone withdrawal. Loss of response rate to IFX was 18% at 1 year. Conclusions Hydrocortisone discontinuation is safe in IBD patients with sustained clinical remission on maintenance therapy with IFX. Our data suggest that routine premedication with hydrocortisone is unnecessary in patients in prolonged remission under IFX maintenance therapy.
Published: 2020

18. Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium

Author: Caroline Trang, Salima Hacein-Bey Abina, Malin Ryner, Florian Deisenhammer, Manuel Comabella, Abiba Doukani, Philippe Broët, Anna Fogdell-Hahn, Julianne Duhaze, Hans-Peter Hartung, Clemens Warnke, Natacha Szely, Delphine Bachelet, Alessandra Vultaggio, Bernd C. Kieseier, Sebastian Spindeldreher, Olivier Brocq, Poul Erik Hyldgaard-Jensen, Michael Auer, Marc Pallardy, Matthieu Allez, Mary Birchler, Tom W J Huizinga, Yehuda Chowers, Yoram Bouhnik, Dorothea Buck-Martin, Elizabeth C. Jury, Amy Loercher, Dan Sikkema, Aude Gleizes, Tobias Derfuss, Jessica J Manson, Guillaume Cadiot, Claudia Sievers, Michael Khalil, Naoimh Donnellan, Raija L.P. Lindberg, Agnès Hincelin Mery, Badreddine Mohand Oumoussa, Enrico Maggi, Martin Soubrier, Kathleen Ingenhoven, Orhan Aktas, Sophie Tourdot, Xavier Montalban, Maria Nachury, Niek de Vries, Timothy P. Hickling, Christophe Richez, Bernhard Hemmer, Franck Carbonnel, Finn Sellebjerg, Jérôme Avouac, Petra Nytrova, Xavier Mariette, Anna Lauren, Signe Hässler, Pierre Dönnes, Eva Havrdova, Michael Guger, Claudia Mauri, BRUNEL, Nadège, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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 National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), CHU Sainte Justine [Montréal], Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), GlaxoSmithKline, Glaxo Smith Kline, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Princesse Grace [Monaco], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Hôpital universitaire Robert Debré [Reims], University of Haifa [Haifa], Universitat Autònoma de Barcelona (UAB), University Hospital Basel [Basel], VU University Medical Center [Amsterdam], Royal Berkshire Hospital, Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Kepler University Hospital, University Hospital Düsseldorf, Charles University [Prague] (CU), Leiden University Medical Center (LUMC), Rigshospitalet [Copenhagen], Copenhagen University Hospital, University College of London [London] (UCL), Karl-Franzens-Universität Graz, Malmö Högskola = Malmö University, University of Basel (Unibas), Università degli Studi di Firenze = University of Florence (UniFI), University College London Hospitals (UCLH), Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU de Bordeaux Pellegrin [Bordeaux], Karolinska Institutet [Stockholm], CHU Clermont-Ferrand, Université de Florence, Fachhochschule Köln, University of Skövde [Sweden], Pfizer, SANOFI Recherche, Hopital Saint-Louis [AP-HP] (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Dusseldorf, Innsbruck Medical University [Austria] (IMU), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Karl-Franzens-Universität [Graz, Autriche], Malmø University, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Graz, AII - Inflammatory diseases, and Clinical Immunology and Rheumatology
Subjects: Male, Physiology, [SDV]Life Sciences [q-bio], Single Nucleotide Polymorphisms, Autoimmune Diseases/drug therapy, Biological Therapy/methods, Arthritis, 030204 cardiovascular system & hematology, Biochemistry, Inflammatory bowel disease, Etanercept, Arthritis, Rheumatoid, Cohort Studies, chemistry.chemical_compound, Medical Conditions, 0302 clinical medicine, Crohn Disease, Antibiotics, Immune Physiology, Medicine and Health Sciences, Prospective Studies, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Immune System Proteins, Antimicrobials, Drugs, Neurodegenerative Diseases, General Medicine, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Biological Therapy, Antibodies, Monoclonal, Humanized/therapeutic use, Neurology, Arthritis, Rheumatoid/drug therapy, Rheumatoid arthritis, Genome-Wide Association Study/methods, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, Immunosuppressive Agents, Interferon beta-1a, Research Article, medicine.drug, Adult, Multiple Sclerosis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Rheumatoid Arthritis, Gastroenterology and Hepatology, Antibodies, Monoclonal, Humanized, Microbiology, Antibodies, HLA-DQ alpha-Chains, Autoimmune Diseases, 03 medical and health sciences, Tocilizumab, Rheumatology, Adalimumab/therapeutic use, Microbial Control, HLA-DQ alpha-Chains/genetics, Rituximab/therapeutic use, Genetics, medicine, Adalimumab, Humans, Antigens, Biological Products/immunology, Pharmacology, Biological Products, Interferon beta-1a/therapeutic use, business.industry, Inflammatory Bowel Disease, Biology and Life Sciences, Proteins, medicine.disease, Demyelinating Disorders, Infliximab, Minor allele frequency, Infliximab/therapeutic use, chemistry, Crohn Disease/drug therapy, Immunosuppressive Agents/therapeutic use, Multiple Sclerosis/drug therapy, Clinical Immunology, Colitis, Ulcerative, Clinical Medicine, Colitis, Ulcerative/drug therapy, business, Genome-Wide Association Study
Abstract: Background Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. Methods and findings The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn’s disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253–0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437–0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616–4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319–3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923–5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139–6.764], p < 1 × 10−5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106–4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. Conclusion In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies., In a multicohort prospective study of patients from 12 countries, Signe Hässler and colleagues investigate clinical and genetic factors associated with development of anti-biopharmaceutical drug antibodies in patients with autoimmune diseases., Author summary Why was this study done? Biopharmaceutical products such as monoclonal antibodies are widely used to treat autoimmune diseases. Biopharmaceutical products may induce the development of antidrug antibodies, which often lead to therapy failure. Patient-related factors that influence the development of antidrug antibodies need to be characterized. What did the researchers do and find? We set up a European multicohort prospective study on 4 autoimmune diseases (multiple sclerosis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis) treated with 8 different biopharmaceutical products. We collected demographic and clinical data and tested antidrug antibodies in longitudinal serum samples from 560 patients. For 457 patients who gave consent, we also collected genetic data. We identified antibiotics and immunosuppressants as negatively associated risk factors and heavy smoking, infections during the study, the HLA-DQA1*05 allele and a minor variant in the CXCL12 chemokine gene associated with increased protein expression as risk factors of antidrug antibody development. What do these findings mean? Our findings suggest that the combination of immunosuppressant and biopharmaceutical therapy could be associated with decreased risk of antidrug antibody occurrence, which has implications for rheumatoid arthritis and inflammatory bowel diseases, for which immunosuppressants are often, but not always, given together with biopharmaceuticals. Patients heterozygotes or homozygotes for the HLA-DQA1*05 allele may have an increased risk of antidrug antibody occurrence associated with biopharmaceutical therapy. The small study size warrants a validation through independent studies, in particular for the genetic findings.
Published: 2020
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19. Real-world use of therapeutic drug monitoring of CT-P13 in patients with inflammatory bowel disease: A 12-month prospective observational cohort study

Author: Pauline Jouet, Laurent Beaugerie, Anne-Laure Pelletier, Robert Benamouzig, Xavier Amiot, Nicolas Petitdidier, Georgia Malamut, Vered Abitbol, Xavier Treton, Aurelien Amiot, Lysiane Marthey, Matthieu Allez, Franck Carbonnel, Yoram Bouhnik, Sylvie Rajca, Anne Bourrier, Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Inflammatory bowel disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Trough Concentration, Prospective Studies, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Antibodies, Monoclonal, Middle Aged, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Infliximab, 3. Good health, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, Drug Monitoring, business, Cohort study, medicine.drug
Abstract: Summary Background Whether therapeutic drug monitoring (TDM) of infliximab should be implemented in daily practice is an ongoing controversy. Aims To assess the real-world use of TDM in an observational multicentre cohort study with consecutive patients with inflammatory bowel disease (IBD) treated with CT-P13. Methods Between September 2015 and December 2016, 364 patients with IBD were treated with CT-P13 in 13 gastroenterology departments and were followed up for 54 weeks. Disease activity, CT-P13 trough concentration and anti-CT-P13 antibody (ACA) were recorded. Results Steroid-free clinical remission rates at week 54 were 67.0% and 56.4% in patients with CD and UC, respectively. CT-P13 trough concentrations were measured in 70.7% of the patients. The mean CT-P13 trough concentration was 4.2 ± 4.3 μg/mL. The presence of ACA was observed in 53 (15.9%) patients. CT-P13 trough concentration was collected in a proactive approach in 62.8% of cases and in a reactive approach in 37.2%. Among patients who submitted to TDM, CT-P13 therapy was optimized in 88.7% of the reactive group and in 22.5% of the proactive group (P Conclusion In a real-world cohort of patients with IBD treated with CT-P13, more than two-thirds of the patients underwent TDM. CT-P13 optimization was much less common in the proactive approach than in the reactive approach.
Published: 2020
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20. Maintenance of remission among patients with inflammatory bowel disease after vedolizumab discontinuation: a multicentre cohort study

Author: Antoine, Martin, Maria, Nachury, Laurent, Peyrin-Biroulet, Yoram, Bouhnik, Stephane, Nancey, Anne, Bourrier, Melanie, Serrero, Mathurin, Fumery, Anthony, Buisson, David, Laharie, Cyrielle, Gilletta, Jerome, Filippi, Matthieu, Allez, Guillaume, Bouguen, Xavier, Roblin, Romain, Altwegg, Nina, Dib, Guillaume, Pineton de Chambrun, Guillaume, Savoye, Franck, Carbonnel, Stephanie, Viennot, Aurelien, Amiot, Guillaume, Lebaut, CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), 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), CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Nice (CHU Nice), Hopital Saint-Louis [AP-HP] (AP-HP), Centre d'Investigation Clinique [Rennes] (CIC), 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), Nutrition, Métabolismes et Cancer (NuMeCan), 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), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-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), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital Charles Nicolle [Rouen], CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Crohn’s disease, vedolizumab, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Antibodies, Monoclonal, Humanized, Lower risk, Inflammatory bowel disease, Vedolizumab, 03 medical and health sciences, Deprescriptions, 0302 clinical medicine, Crohn Disease, Gastrointestinal Agents, Recurrence, inflammatory bowel disease, Internal medicine, medicine, Humans, 030212 general & internal medicine, Retrospective Studies, ulcerative colitis, Crohn's disease, business.industry, Remission Induction, Hazard ratio, Gastroenterology, Patient Preference, Retrospective cohort study, General Medicine, medicine.disease, Ulcerative colitis, 3. Good health, Discontinuation, C-Reactive Protein, Retreatment, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, business, Follow-Up Studies, medicine.drug
Abstract: Background and Aim It is unclear whether vedolizumab therapy can be discontinued in patients with inflammatory bowel disease [IBD] after achieving steroid-free clinical remission. The aim was to assess the risk of relapse after vedolizumab therapy was discontinued. Methods This was a retrospective observational study, collecting data from 21 tertiary centres affiliated with the GETAID from January 2017 to April 2019. Consecutive patients with IBD, who were in steroid-free clinical remission for at least 3 months and were treated with vedolizumab for at least 6 months, were included at the time of vedolizumab discontinuation. Results A total of 95 patients [58 with Crohn’s disease] discontinued vedolizumab after a median duration of therapy of 17.5 [10.6–25.4] months. After a median follow-up period of 11.2 [5.8–17.7] months, 61 [64%] patients experienced disease relapse. The probabilities of relapse-free survival were 83%, 59%, and 36% at 6, 12, and 18 months, respectively. According to the multivariate analysis, a C-reactive protein level less than 5 mg/L at vedolizumab discontinuation (hazard ratio [HR] = 0.56, 95% confidence interval [CI] [0.33–0.95], p = 0.03) and discontinuation due to patients’ elective choice (HR = 0.41, 95% CI [0.21–0.80], p = 0.009) were significantly associated with a lower risk of relapse. Re-treatment with vedolizumab was noted in 24 patients and provided steroid-free clinical remission in 71% and 62.5% at Week 14 and after a median follow-up of 11.0 [5.4–13.3] months, respectively, without any infusion reactions. Conclusions In this retrospective study, two-thirds of patients with IBD treated with vedolizumab experienced relapse within the first year after vedolizumab discontinuation. Re-treatment with vedolizumab was effective in two-thirds of patients.
Published: 2020
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21. Care of the Patient with IBD Requiring Hospitalization During the COVID-19 Pandemic

Author: Phillip Fleshner, David T. Rubin, Matthieu Allez, Richard B. Gearry, and Peter L. Lakatos
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Letter to the editor, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Population, MEDLINE, Context (language use), Disease, Inflammatory bowel disease, Betacoronavirus, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Health care, Pandemic, Medicine, Humans, education, Intensive care medicine, Letter to the Editor, Pandemics, AcademicSubjects/MED00260, education.field_of_study, Clinical Laboratory Techniques, business.industry, Transmission (medicine), SARS-CoV-2, Gastroenterology, COVID-19, General Medicine, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, Hospitalization, 030220 oncology & carcinogenesis, Concomitant, 030211 gastroenterology & hepatology, Original Article, Coronavirus Infections, business
Abstract: The management of IBD has been highly affected in the context of the COVID-19 pandemic, with restriction of hospitalisations and unprecedented redeployment of health care resources. Hospital admissions of IBD patients should be limited to reduce the risks of coronavirus transmission. However, delaying hospitalisation of IBD patients with severe or complicated disease may increase the risk of poor outcomes. Delaying surgery in some cases may increase the risk of disease progression, postoperative morbidity, and disease complications. IBD patients who are infected with SARS-CoV-2 may have a higher risk of poor outcomes than the general population, potentially related to concomitant medications, especially corticosteroids. There is no evidence today that IBD patients with COVID-19 have worse outcomes if they receive immunosuppressant medications including thiopurines, biologics, and novel small molecules. This article summarises recommendations by the international membership of IOIBD regarding hospitalisations of IBD patients, either for active or complicated IBD or for severe COVID-19, and for management of IBD patients according to SARS-CoV-2 infectious status.
Published: 2020

22. Rare cause of rectal stenosis in a patient with long-term use of Infliximab and Mercaptopurine for ulcerative colitis

Author: Charlotte Gardair, Jean-Marc Gornet, My-Linh Tran-Minh, Matthieu Allez, and Nassim Hammoudi
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Combination therapy, Constriction, Pathologic, Proctoscopy, Risk Assessment, Severity of Illness Index, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Pharmacotherapy, Internal medicine, Severity of illness, medicine, Humans, Colitis, Sigmoidoscopy, Dose-Response Relationship, Drug, Mercaptopurine, business.industry, Biopsy, Needle, Middle Aged, medicine.disease, Immunohistochemistry, Ulcerative colitis, Infliximab, Golimumab, Rectal Diseases, 030104 developmental biology, Colitis, Ulcerative, Drug Therapy, Combination, 030211 gastroenterology & hepatology, business, Follow-Up Studies, medicine.drug
Abstract: A 58-year-old, non-smoker male patient with no family history was followed up since 2002 for ulcerative colitis (UC) located in the rectosigmoid. He was initially treated by salicylates alone until November 2008. Mercaptopurine was started in August 2009 for steroid dependence with primary failure despite adequate 6 thioguanine nucleotides (6 TGN) level. He was included in February 2010 in the PURSUIT trial testing Golimumab with only partial response. A combination therapy with Mercaptopurine and Infliximab was then started in December 2010 with a long-term clinical, biological and endoscopic steroid-free remission. A pan-chromoendoscopy performed in June 2016 showed a complete mucosal healing with no histological activity …
Published: 2018
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23. Inflammatory bowel disease drastically affects the prognosis of patients treated for peritoneal metastases with combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A multicenter study

Author: Clarisse Eveno, Diane Goéré, Nassim Hammoudi, Jérôme Lambert, Thomas Aparicio, Marc Pocard, Matthieu Allez, Nelson Lourenco, Marianne Maillet, Jean-Marc Gornet, and Olivier Glehen
Subjects: medicine.medical_specialty, Colorectal cancer, business.industry, General Medicine, Disease, medicine.disease, Gastroenterology, Inflammatory bowel disease, digestive system diseases, Oxaliplatin, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Cohort, medicine, Peritoneal Cancer Index, 030211 gastroenterology & hepatology, Surgery, Hyperthermic intraperitoneal chemotherapy, Cytoreductive surgery, business, medicine.drug
Abstract: Background Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected patients with peritoneal metastases (PM) of intestinal origin. There is an increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical approach in IBD patients is unknown. Methods IBD patients with operated PM complicating CRC or SBA were extracted from a French national multicenter prospective database of patients who underwent surgery for PM in HIPEC expert centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were compared with a cohort of 234 patients who had the same surgery for sporadic colon cancer. Results 14 patients (male 57%, median age 40 years, 12 Crohn's disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7; range 1–30). The control group had the same characteristics except an older age at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91 to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly lower in IBD patients. Six of the 11 patients presented major surgical morbidity with no impact on post-operative treatment. Conclusion CCRS followed by HIPEC is less effective in IBD patients with resectable PM complicating CRC or SBA. More careful selection of those patients is needed.
Published: 2018
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24. 775d Ustekinumab Versus Adalimumab for Induction and Maintenance Therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE Study

Author: Stephen B. Hanauer, Oksana Shchukina, Matthieu Allez, Edward V. Loftus, Long-Long Gao, Andrew Greenspan, Remo Panaccione, Christopher Gasink, James D. Lewis, Silvio Danese, Bruce E. Sands, Emese Mihály, Timothy Hoops, J Izanec, Vipul Jairath, Peter M. Irving, Tanja Kuehbacher, William J. Sandborn, and Ellen Scherl
Subjects: Moderate to severe, medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Gastroenterology, medicine.disease, Maintenance therapy, Internal medicine, Ustekinumab, medicine, Adalimumab, business, medicine.drug
Published: 2021
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25. Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD

Author: Ioannis E. Koutroubakis, Simon Travis, Edward V. Loftus, Bruce E. Sands, Yehuda Chowers, Arthur Kaser, Antonino Spinelli, Maria T. Abreu, Gerassimos J. Mantzaris, Gerhard Rogler, Parambir S. Dulai, Milan Lukas, Dan Turner, Ailsa Hart, Colm O'Morain, Jonas Halfvarson, Matthieu Allez, Severine Vermeire, Silvio Danese, Geert R. D'Haens, William J. Sandborn, Walter Reinisch, Siew C. Ng, Subrata Ghosh, Flavio Steinwurz, Pia Munkholm, Jean-Frederic Colombel, Remo Panaccione, Stefan Schreiber, David B. Sachar, Laurent Peyrin-Biroulet, Julián Panés, Vipul Jairath, Aswhin N. Ananthakrishnan, Peter R. Gibson, Wolfgang Kruis, Catherine Le Berre, Iris Dotan, David T. Rubin, Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), SPIRIT-IOIBD study group: William J Sandborn, Jean-Frédéric Colombel, David Rubin, Yehuda Chowers, Walter Reinisch, Stefan Schreiber, Matthieu Allez, Geert D'Haens, Subrata Ghosh, Ioannis E Koutroubakis, Peter Gibson, Jonas Halfvarson, Ailsa Hart, Arthur Kaser, Pia Munkholm, Wolfgang Kruis, Severine Vermeire, Edward V Loftus Jr, Milan Lukas, Gerassimos J Mantzaris, Colm O'Morain, Julian Panes, Gerhard Rogler, Antonino Spinelli, Bruce E Sands, Aswhin N Ananthakrishnan, Siew C Ng, David Sachar, Simon Travis, Flavio Steinwurz, Dan Turner, Parambir S Dulai, Vipul Jairath, Iris Dotan, Maria Abreu, Remo Panaccione, Silvio Danese, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Arnone, Djésia
Subjects: 0301 basic medicine, medicine.medical_specialty, Consensus, Time Factors, SF-36, Endpoint Determination, [SDV]Life Sciences [q-bio], education, Crohn's Disease, Disease, Severity of Illness Index, Inflammatory bowel disease, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Cost of Illness, Crohn Disease, Quality of life, medicine, Humans, Ulcerative Colitis, Fecal incontinence, Disease Severity, Intensive care medicine, Clinical Trials as Topic, Crohn's disease, Hepatology, business.industry, Gastroenterology, Short bowel syndrome, medicine.disease, Ulcerative colitis, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], Functional Status, Treatment Outcome, 030104 developmental biology, Research Design, Quality of Life, Disease Progression, Colitis, Ulcerative, 030211 gastroenterology & hepatology, medicine.symptom, business, Fecal Incontinence, Crohn’s Disease
Abstract: International audience; Background and aims: Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are chronic and disabling disorders. Prospective disease-modification trials to prevent disease progression are eagerly awaited. However, disease progression is not clearly defined. The objective of the Selecting End PoInts foR Disease-ModIfication Trials (SPIRIT) initiative was to achieve international expert consensus on the endpoints to be used in future IBD-disease modification trials.Methods: This initiative under the auspices of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) began with a systematic literature search to evaluate the current evidence on the definition of disease progression in IBD. On October 22, 2019, a consensus meeting took place during the United European Gastroenterology Week (UEGW) Congress in Barcelona, during which predefined proposed statements were discussed in a plenary session and voted on anonymously. Agreement was defined as at least 75% of participants voting for any one statement.Results: The group agreed that the ultimate therapeutic goal in both CD and UC is to prevent disease impact on patient's life (health-related quality of life, disability, fecal incontinence), midterm complications (encompass bowel damage in CD, IBD-related surgery and hospitalizations, disease extension in UC, extraintestinal manifestations, permanent stoma, short bowel syndrome), and long-term complications (gastrointestinal and extraintestinal dysplasia or cancer, mortality).Conclusions: Recommendations on which goals to achieve in disease-modification trials for preventing disease progression in patients with IBD are proposed by the SPIRIT consensus. However, these recommendations will require validation in actual clinical studies before implementation in disease-modification trials.
Published: 2021
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26. Autologous Haematopoietic Stem Cell Transplantation (AHSCT) in Severe Crohn’s Disease: A Review on Behalf of ECCO and EBMT

Author: John A. Snowden, Francesco Onida, Montserrat Rovira, Julián Panés, Daan Dierickx, Peter Hasselblatt, Severine Vermeire, Riccardo Saccardi, Elena Ricart, Marrow Transplantation, James O. Lindsay, Tobias Alexander, Azucena Salas, Sandro Ardizzone, Christopher J. Hawkey, Matthieu Allez, Ebmt (Jacie), Jürgen Finke, and Majid Kazmi
Subjects: 0301 basic medicine, medicine.medical_specialty, Context (language use), Disease, Severity of Illness Index, Transplantation, Autologous, Inflammatory bowel disease, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Crohn Disease, Quality of life, Severity of illness, medicine, Humans, Intensive care medicine, Crohn's disease, business.industry, Patient Selection, Hematopoietic Stem Cell Transplantation, Gastroenterology, General Medicine, medicine.disease, Clinical trial, Transplantation, 030104 developmental biology, 030211 gastroenterology & hepatology, business
Abstract: Despite the major recent progress in the treatment of Crohn's disease [CD], there is a subset of patients in whom the disease runs an aggressive course with progressive tissue damage requiring early and repeated surgical management. Increasing evidence supports sustained and profound improvement in gastrointestinal parameters and quality of life following high-dose immunosuppressive therapy and autologous haematopoietic stem cell transplantation [AHSCT] compared to standard therapy in this context. In addition, international transplant registry data reflect the use of AHSCT in CD outside of trials in selected patients. However, AHSCT may be associated with significant treatment-related complications with risk of transplant-related mortality. In a joint initiative, the European Crohn's and Colitis Organisation [ECCO] and the European Society for Blood and Marrow Transplantation [EBMT] have produced a state-of-the-art review of the rationale, evaluation, patient selection, stem cell mobilization and transplant procedures and long-term follow up. Given the unique spectrum of issues, we recommend that AHSCT should only be performed in experienced centres with expertise in both haematological and gastroenterological aspects of the procedure. Where possible, patients should be enrolled on clinical trials and data registered centrally. Future development should be coordinated at both national and international levels.
Published: 2018
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27. Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience

Author: Anne Bourrier, Matthieu Allez, Xavier Roblin, Pauline Wils, Aurelien Amiot, Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif, Mathurin Fumery, Vered Abitbol, Pierre Michetti, Bernard Flourié, A Buisson, Bernard Duclos, Benoit Coffin, Guillaume Bouguen, Hedia Brixi, Yoram Bouhnik, D. Laharie, Mélanie Serrero, Benjamin Pariente, Laurent Peyrin-Biroulet, Marion Simon, and Jérôme Filippi
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Drug Resistance, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Refractory, Pregnancy, Internal medicine, Ustekinumab, medicine, Humans, Pharmacology (medical), Adverse effect, Retrospective Studies, Crohn's disease, Hepatology, Tumor Necrosis Factor-alpha, business.industry, Gastroenterology, Endoscopy, Retrospective cohort study, medicine.disease, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, business, Follow-Up Studies, Cohort study, medicine.drug
Abstract: Background Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. Aim To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. Methods We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. Results Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure-free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure-free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). Conclusion In this cohort of refractory CD patients receiving long-term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.
Published: 2018
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28. Effect of PF-00547659 on Central Nervous System Immune Surveillance and Circulating beta 7+T Cells in Crohn's Disease: Report of the TOSCA Study

Author: Richard M. Ransohoff, Olaf Stüve, Harald Vogelsang, Sunday Rivers, Clare Robert A, Kenneth J. Gorelick, Fabio Cataldi, Mina Hassan-Zahraee, Pierre Desreumaux, Geert R. D'Haens, John B. Cheng, Annamarie Kaminski, Yanhua Zhang, Alaa Ahmad, William J. Sandborn, Vivek Pradhan, Severine Vermeire, Matthieu Allez, André Van Gossum, Daniel C. Baumgart, Matthew O Sikpi, Gail M. Comer, Walter Reinisch, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology and Hepatology
Subjects: 0301 basic medicine, Adult, Central Nervous System, Male, Crohn’s disease, Integrin beta Chains, Adolescent, Lymphocyte, medicine.medical_treatment, T cell, T-Lymphocytes, Antibodies, Monoclonal, Humanized, Inflammatory bowel disease, 03 medical and health sciences, Young Adult, Natalizumab, Crohn Disease, T-Lymphocyte Subsets, inflammatory bowel disease, medicine, Humans, Gastro-entérologie, MAdCAM-1, Lymphocyte Count, Immunologic Surveillance, Crohn's disease, business.industry, Progressive multifocal leukoencephalopathy, Multiple sclerosis, immune surveillance, PF-00547659, Gastroenterology, Leukoencephalopathy, Progressive Multifocal, Immunosuppression, General Medicine, Original Articles, Middle Aged, medicine.disease, 3. Good health, Immune surveillance, 030104 developmental biology, medicine.anatomical_structure, Immunology, Female, business, Immunosuppressive Agents, medicine.drug
Abstract: Background and Aims: Progressive multifocal leukoencephalopathy [PML], a brain infection associated with anti-integrin drugs that inhibit lymphocyte translocation from bloodstream to tissue, can be fatal. Decreased central nervous system [CNS] immune surveillance leading to this infection has been reported in patients with multiple sclerosis or Crohn's disease treated with antiintegrin antibody natalizumab. PF-00547659 is an investigational human monoclonal antibody for inflammatory bowel disease, targeted against α4β7-mucosal addressin cell-adhesion molecule-1 [the integrin ligand selectively expressed in the gut]. We hypothesised that this selective agent would not affect central nervous system immune surveillance. Methods: Cerebrospinal fluid from five healthy volunteers, and from 10 patients with Crohn's disease previously treated with immunosuppressants, was evaluated to assess the feasibility of the study. Subsequently, 39 patients with active Crohn's disease and previous immunosuppression were evaluated over 12 weeks of PF-00547659-induction therapy. We measured total lymphocytes, T cell subsets in cerebrospinal fluid, and circulating β7+ memory cells. Disease activity was assessed using the Harvey-Bradshaw Index. Results: Patients treated with PF-00547659 had no reduction of cerebrospinal fluid lymphocytes, T-lymphocyte subsets, or CD4:CD8 ratio, whereas circulating β7+ memory cells increased significantly. A total of 28/35 [80%] patients had a clinical response and 27/34 [79%] had disease remission. Treatment-related adverse events, none serious, were reported in 23/49 [47%] patients. Conclusions: In patients with active Crohn's disease, natalizumab therapy increases the risk for PML, and the increased risk is thought to be associated with iatrogenic leukopenia within the CNS. PML under PF-00547659 may be a lesser concern, as this agent did not reduce lymphocytes or T cell subsets in the cerebrospinal fluid., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2018
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29. COVID‐19–Related IgA Vasculitis

Author: Constance Delaugerre, Jérôme Le Goff, Jean-Michel Molina, Evangeline Pillebout, Anne Marie Zagdanski, Jules Bayart, Marie Laure Chaix Baudier, Maxime Battistella, Blandine Denis, Matthieu Allez, Jean-David Bouaziz, Caroline Gatey, and Ingrid Lazaridou
Subjects: 0301 basic medicine, Coronavirus disease 2019 (COVID-19), business.industry, Immunology, medicine.disease, Serology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, IgA vasculitis, Rheumatology, medicine, Adalimumab, Immunology and Allergy, Ileitis, Tumor necrosis factor alpha, 030212 general & internal medicine, Young adult, Letters to the Editor, business, Vasculitis, Letter to the Editor, medicine.drug
Abstract: IgA vasculitis is a systemic small‐vessel vasculitis which may be triggered by different microorganisms. IgA vasculitis cases have been reported in patients with immune‐mediated inflammatory disorders treated with TNF inhibitors. Here we report the case of a young Crohn’s disease patient in clinical remission under adalimumab admitted for an IgA vasculitis, with an extended ileitis, and a positive PCR testing for Covid‐19. Serum IgA levels were markedly increased and serology for Covid‐19 was weakly positive for IgA. Even if we cannot prove the causality of Covid‐19, it is remarkable to note that this case of IgA vasculitis was associated with high IgA levels in the serum and the Covid‐19 serology was positive only for IgA.
Published: 2020
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30. Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease

Author: Philippe Seksik, Xavier Treton, Mathurin Fumery, Claire Auzolle, Nicolas Barnich, Lionel Le Bourhis, Benjamin Pariente, Anthony Buisson, Loic Brot, Stéphane Nancey, Harry Sokol, Carmen Stefanescu, Matthieu Allez, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Clermont-Ferrand, CHU Amiens-Picardie, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, This study has been supported by grants from MSD France, Association Francois Aupetit, the Helmsley Charitable Trust and Inserm., Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AgroParisTech, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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 la Recherche Agronomique (INRA), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Universitaire Clermont Ferrand, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Autophagie infections immunité – Autophagy Infection Immunity, 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)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Adult, Male, medicine.medical_specialty, Firmicutes, Disease, Gut flora, Gastroenterology, digestive system, Endoscopy, Gastrointestinal, Ileal resection, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Crohn Disease, Ileum, Recurrence, Risk Factors, Internal medicine, Proteobacteria, medicine, microbiota, Humans, Postoperative Period, Prospective Studies, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Crohn's disease, biology, business.industry, Lachnospiraceae, Healthy subjects, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, mucosa-associated, Middle Aged, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Gastrointestinal Microbiome, Cohort, 030211 gastroenterology & hepatology, Female, business, Ileal mucosa
Abstract: ObjectiveFollowing ileal resection for Crohn’s disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence.Patients and methodsIleal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France.ResultsIleal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors.ConclusionSurgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.
Published: 2020
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31. Postoperative Endoscopic Recurrence on the Neoterminal Ileum But Not on the Anastomosis Is Mainly Driving Long-Term Outcomes in Crohn's Disease

Author: Madeleine Bezault, Philippe Seksik, Mathurin Fumery, Nassim Hammoudi, Benjamin Pariente, Anthony Buisson, Stéphane Nancey, Claire Auzolle, Lionel Le Bourhis, Gilles Boschetti, My-Linh Tran Minh, Xavier Treton, Matthieu Allez, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Crohn's disease, medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, Gold standard, Gastroenterology, Ileum, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Anastomosis, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Endoscopy, Surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Interquartile range, 030220 oncology & carcinogenesis, medicine, Long term outcomes, 030211 gastroenterology & hepatology, In patient, business, ComputingMilieux_MISCELLANEOUS
Abstract: Early ileocolonoscopy within the first year after surgery is the gold standard to evaluate recurrence after ileocolonic resection for Crohn's disease (CD). The aim of the study was to evaluate the association between the presence and severity of anastomotic and ileal lesions at early postoperative ileocolonoscopy and long-term outcomes. The REMIND group conducted a prospective multicenter study. Patients operated for ileal or ileocolonic CD were included. An ileocolonoscopy was performed 6 months after surgery. An endoscopic score describing separately the anastomotic and ileal lesions was built. Clinical relapse was defined by the CD-related symptoms, confirmed by imaging, endoscopy or therapeutic intensification; CD-related complications; or subsequent surgery. Among 225 included patients, long-term follow-up was available in 193 (median follow-up: 3.82 years [interquartile range: 2.56-5.41]). Median clinical recurrence-free survival was 47.6 months. Clinical recurrence-free survival was significantly shorter in patients with ileal lesions at early postoperative endoscopy whatever their severity was (I(1) or I(2,3,4)) as compared to patients without ileal lesions (I(0)) (I(0) vs I(2,3,4): P = 0.0003; I(0) vs I(1): P = 0.0008 and I(1) vs I(2,3,4): P = 0.43). Patients with exclusively ileal lesions (A(0)I(1,2,3,4)) had poorer clinical long-term outcomes than patients with exclusively anastomotic lesions (A(1,2,3)I(0)) (P = 0.009). A score describing separately the anastomotic and ileal lesions might be more appropriate to define postoperative endoscopic recurrence. Our data suggest that patients with ileal lesions, including mild ones (I(1)), could beneficiate from treatment step-up to improve long-term outcomes.
Published: 2020
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32. T cell clonal expansions in ileal Crohn’s disease are associated with smoking behaviour and postoperative recurrence

Author: Benjamin Pariente, Azucena Salas, Xavier Treton, Matthieu Allez, Stéphane Nancey, Victor Chardiny, Anthony Buisson, Mathurin Fumery, Harry Sokol, Nicolas Barnich, Marjolaine Ngollo, Hugo Bottois, Carmen Stefanescu, Philippe Seksik, Ana Maria Corraliza, Claire Auzolle, Lionel Le Bourhis, Kevin Perez, Service d'hépato-gastro-entérologie, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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)-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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Helmsley Charitable Trust Association Francois Aupetit MSD France laboratories, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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)-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), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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 la Recherche Agronomique (INRA)
Subjects: Adult, Male, medicine.medical_specialty, Microarray, T cell, Receptors, Antigen, T-Cell, Gastroenterology, Cohort Studies, Pathogenesis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Recurrence, Internal medicine, medicine, Humans, Cytotoxic T cell, Postoperative Period, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Crohn's disease, medicine.diagnostic_test, business.industry, Smoking, T-cell receptor, Area under the curve, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Ileitis, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Endoscopy, Treatment Outcome, medicine.anatomical_structure, Female, 030211 gastroenterology & hepatology, business
Abstract: T cell clonal expansions are present in the inflamed mucosa of patients with Crohn’s disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection.MethodsT cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively.ResultsTCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment.ConclusionClonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven.Trial registration numberNCT03458195.
Published: 2019
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33. The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn's disease refractory to anti-tumour necrosis factor

Author: Julien Kirchgesner, Yoram Bouhnik, Aurelien Amiot, Franck Carbonnel, Antoine Meyer, Laurent Beaugerie, Xavier Treton, Hadrien Alric, and Matthieu Allez
Subjects: Adult, Male, medicine.medical_specialty, Combination therapy, Antibodies, Monoclonal, Humanized, Gastroenterology, Vedolizumab, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Refractory, Crohn Disease, Internal medicine, Ustekinumab, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Retrospective Studies, Crohn's disease, Hepatology, business.industry, Tumor Necrosis Factor-alpha, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, 030211 gastroenterology & hepatology, Female, business, Cohort study, medicine.drug
Abstract: Background There is no head-to-head trial comparing ustekinumab and vedolizumab in patients with Crohn's disease (CD) refractory to anti-tumour necrosis factor (anti-TNF). Aim To compare the effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti-TNF in a multicentre retrospective observational cohort. Methods All consecutive patients with CD refractory or intolerant to anti-TNF who initiated either vedolizumab or ustekinumab were included between May 2014 and August 2018. Clinical remission, steroid-free clinical remission (SFCR) and treatment persistence were assessed at week 48 with intention-to-treat analysis and propensity scores weighted comparison. Results A total of 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. At week 48, ustekinumab was associated with a higher clinical remission rate (54.4% vs 38.3%; odds ratios, OR = 1.92, 95% CI [1.09-3.39]) and treatment persistence (71.5% vs 49.7%; OR = 2.54, 95% CI [1.40-4.62]) than vedolizumab. The rate of SFCR did not differ significantly between ustekinumab and vedolizumab (44.7% vs 34.0%; OR = 1.57, 95% CI [0.88-2.79]). Subgroup analyses showed that ustekinumab was associated with a higher clinical remission rates at week 48 in patients with ileal location (OR = 3.49, 95% CI [1.33-9.17) and penetrating behaviour (OR = 6.58, 95% CI [1.91-22.68]). Regardless of the treatment group, combination therapy at initiation was associated with a higher clinical remission rate at week 48 (OR = 1.93, 95% CI [1.09-3.43]). Conclusion This study suggests that ustekinumab is associated with a higher rate of clinical remission and treatment persistence than vedolizumab after 48 weeks of follow-up, in patients with CD refractory or intolerant to anti-TNF. The rate of SFCR was not significantly different.
Published: 2019

34. Imatinib in Refractory Crohn Disease: A Series of 6 Cases

Author: Matthieu Allez, Anna Boctor, Jean-Pierre Hugot, Marc Bellaiche, Christine Martinez-Vinson, and Thierry Leblanc
Subjects: Crohn's disease, medicine.medical_specialty, Series (stratigraphy), business.industry, Crohn disease, Gastroenterology, Imatinib, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Imatinib mesylate, Refractory, hemic and lymphatic diseases, Internal medicine, Medicine, 030211 gastroenterology & hepatology, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Biologics have revolutionized Crohn disease (CD) treatment. Nevertheless, absence or loss of response is frequent and alternative therapeutic options may be necessary. Imatinib is a tyrosine kinase inhibitor that is used in chronic myeloid leukemia. A positive impact on CD in 2 patients with chronic myeloid leukemia treated with imatinib led us to propose the drug in 4 additional patients with refractory CD. Four out of these 6 patients reached clinical and endoscopic remission at a median time of 3 months. Remission was maintained for 9 months to 7 years. Imatinib may thus be considered as new therapeutic options for refractory CD. We report 6 CD patients treated with imatinib. Two of them because of a leukemia and 4 because of a disease refractory to all medical options. Four patients experienced full and sometimes prolonged remission of their digestive disease.
Published: 2019
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35. Severe gastrointestinal toxicity of MEK inhibitors

Author: Philippe Bertheau, Cécile Pagès, Céleste Lebbé, Nelson Lourenco, Nadim Mourad, Julie Delyon, Matthieu Allez, Clara Allayous, A. Ballon, Barouyr Baroudjian, and Pirayeh Eftekhari
Subjects: 0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, Skin Neoplasms, Databases, Factual, Nausea, Pyridones, MAP Kinase Kinase 1, Antineoplastic Agents, Dermatology, Pyrimidinones, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Gastrointestinal perforation, Internal medicine, Medicine, Humans, Enzyme Inhibitors, Adverse effect, Melanoma, Aged, Retrospective Studies, Trametinib, Cobimetinib, business.industry, Binimetinib, Middle Aged, medicine.disease, Discontinuation, Gastrointestinal Tract, 030104 developmental biology, Treatment Outcome, Oncology, chemistry, 030220 oncology & carcinogenesis, Vomiting, Azetidines, Benzimidazoles, Female, medicine.symptom, business
Abstract: Gastrointestinal toxicities of MEK inhibitors in melanoma patients are frequent. In clinical trials, the most common digestive adverse events were nausea, vomiting, and diarrhoea. However, severe toxicities such as colitis and gastrointestinal perforation, some with fatal outcomes, have been reported. These rare but severe adverse events are not well described. We performed a retrospective analysis of all patients with stage IV and unresectable stage III melanoma treated with a MEK inhibitors at Saint-Louis Hospital, Paris, between 1 August 2013 and 15 October 2018. Among 119 patients exposed to MEK inhibitors, 78 were treated with trametinib, 19 with cobimetinib, four with binimetinib, and 18 patients with two different MEK inhibitors at separate times. All grade digestive adverse events were observed in 39 (32.7%) patients. Grade 3 and 4 adverse events occurred in 6 (5%) patients: 2 (1.7%) developed perforations, 3 (2.5%) had colitis and 1 (0.8%) had grade 4 diarrhoea. These adverse events were all reversible following a permanent discontinuation of the MEK inhibitors, or a temporary interruption followed by resumption at a dose lower than conventional posology. There were no fatal outcomes; however one patient had a permanent ileostomy. The mechanism underlying these toxicities is not well known. Clinicians should be aware of such toxicities.
Published: 2019

36. Association Between Microscopic Lesions at Ileal Resection Margin and Recurrence After Surgery in Patients With Crohn’s Disease

Author: Alexandra Traverse-Glehen, Nassim Hammoudi, Olivier Corcos, Philippe Marteau, Julien Loreau, Mariane Maillet, Martine Leconte, Jonathan Catry, Yves Francois, Najim Chafai, Xavier Dray, Marjolaine Ngollo, Philippe Seksik, Pierre Cattan, Benjamin Pariente, Nicolas Munoz-Bongrand, Peggy Falgon, Stéphane Nancey, Nathan Beaupel, Isabelle Nion-Larmurier, Andrée Nisard, Christophe Attencourt, Emmanuel Tiret, Ulrika Chaput, Denis Chatelain, Marion Chauvenet, Dominique Cazals-Hatem, Eddy Cotte, Laurent Beaugerie, Madeleine Bezault, Mircea Chirica, Gilles Boschetti, Sarah Boyer, Loic Brot, Julien Kirchgesner, Hugo Bottois, Anne Dubois, Magali Svrcek, Yoram Bouhnik, Jean-Marc Gornet, Rachid Kaci, Brice Gergaud, Carmen Stefanescu, Helene Corte, Claire Auzolle, Jean-Louis Dupas, Juliette Joubert Zakeyh, Leila Chedouba, Amine Rahili, Elodie Quévrain, Charles Sabbagh, Lionel Le Bourhis, Maria Nachury, Anne Bourrier, Nathalie Guedj, Florence Renaud, Helena Hadjisavvas, Charlotte Gardair, Gilles Bommelaer, Céline Grand, Xavier Treton, Xavier Jouven, Anthony Buisson, Jérémie H. Lefevre, Paul Hofmann, Stéphanie Patouraux, Jérôme Filippi, Xavier Hébuterne, Driffa Moussata, Clotilde Baudry, Nelson Lourenco, Marion Goutte, Harry Sokol, Victor Chardiny, My-Linh Tran-Minh, Bernard Flourié, Pierre Desreumaux, Catherine Godfraind, Coralie Sommeville, Mathurin Fumery, Nicolas Barnich, Joëlle Bonnet, Anne-Laure Charlois, Dilek Coban, Leon Magiorri, Yves Panis, Matthieu Allez, Jean-François Fléjou, Franck Brazier, M. Ferron, Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Département de Pathologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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 la Recherche Agronomique (INRA), Hôpital Beaujon [AP-HP], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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)-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), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Cryptitis, Ileum, REMIND Trial, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Recurrence, Interquartile range, medicine, Humans, Prospective Studies, Colectomy, Digestive System Surgical Procedures, Outcome, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Prognostic Factor, IBD Surgery, Anastomosis, Surgical, Gastroenterology, Margins of Excision, Histology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Odds ratio, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Endoscopy, Surgery, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Complication, business
Abstract: International audience; Background and AimsDifferent types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn’s disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence.MethodsWe collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery.ResultsSix months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026).ConclusionIn patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.
Published: 2019
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37. Serologic Response to Messenger RNA Coronavirus Disease 2019 Vaccines in Inflammatory Bowel Disease Patients Receiving Biologic Therapies

Author: Julio Ramos, Drew Helmus, Brianne Phillipe, Severine Vermeire, Stela Sota, Darwin Jimenez, Vicky Martinez Pazos, Matthieu Allez, Pamela Reyes-Mercedes, Stephanie Gold, David T. Rubin, Jessica A Neil, James O. Lindsay, Xin Chen, Siew C. Ng, Krystal L. Ching, Mark S. Silverberg, Reema Navalurkar, Ken Cadwell, Natalia Herrera, Sacha Gnjatic, Michael Tankelevich, Giulia Roda, Jonas Halfvarson, Maria T. Abreu, Lucie Bernard, Sara Nunez, Kenji Watanabe, Mericien Venzon, Xiaomin Yao, Walter Reinisch, Jack Satsangi, Michelle Mendiolaza, Stephanie Stanley, Vanessa Barcessat, Flavio Steinwurz, Rebekah E. Dixon, Vineet Ahuja, Jean-Frederic Colombel, Kevin Tuballes, Kyung Ku Jang, and Serre-Yu Wong
Subjects: Messenger RNA, Hepatology, biology, business.industry, Gastroenterology, Case-control study, RNA, medicine.disease_cause, medicine.disease, Inflammatory bowel disease, Serology, Immunology, medicine, biology.protein, Tumor necrosis factor alpha, Antibody, business, Coronavirus
Published: 2021
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38. POS1236 IMPACT OF COVID-19 ON INITIATION AND RENEWAL OF BIOTHERAPIES AND TARGETED SYNTHETIC TREATMENTS

Author: L. Perra, Milka Maravic, Simon Pilet, Matthieu Allez, Vincent Descamps, and Pascal Richette
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Abatacept, Immunology, Hydroxychloroquine, medicine.disease, Gastroenterology, General Biochemistry, Genetics and Molecular Biology, Subcutaneous injection, chemistry.chemical_compound, Tocilizumab, Rheumatology, chemistry, Internal medicine, Psoriasis, medicine, Immunology and Allergy, Methotrexate, In patient, business, medicine.drug
Abstract: Background:During the epidemic’s peak of COVID-19, scientific societies published recommendations on biotherapy and targeted synthetic treatment (B/TST) use in patients with chronic articular inflammatory diseases, inflammatory bowel diseases, and psoriasis.Objectives:The objective was to evaluate the impact of COVID-19 in France on initiation and renewal of B/TST.Methods:LRx contains all anonymized medication dispenses prescribed in outpatient care in a representative panel of French retails pharmacies, including data of near 40 million patients. The impact of B/TST initiation and renewal were studied using 2019 as reference and dispense deliveries data of pharmacies with regular flew in order to perform the comparison. B/TST considered were abatacept, anti-TNF, anti-IL6, anti-IL17, anti-IL12/23 or anti-IL23, JAK inhibitors (JAKi) and other classes such as aprelimast, aminosalicylates (AS), hydroxychloroquine (HCQ), and methotrexate (MTX). A treatment initiated was defined as a treatment not delivered in the past 12 months, and conversely for a treatment renewal. Results were presented as raw one and expressed in percentage of patients having at least one B/TST delivery in each therapeutic classes of interest in 2020 compared to 2019 used as reference year (period from week 12 to week 19 considered and corresponding to the lockdown period in France).Results:During the lockdown period, a decrease in initiation was observed for patients treated with: abatacept (405 in 2019 vs 227 in 2020: -44%, pConclusion:During the epidemic’s peak, initiation of AS, MTX, biotherapies (except for tocilizumab), and JAKi dramatically decreased without impacting their renewal. Two treatments were mainly initiated, tocilizumab probably due to a switch from intravenous to subcutaneous injection and HCQ in relation to its presumably effect on COVID-19. Overall, recommendations from scientific societies have been followed.Disclosure of Interests:None declared
Published: 2021
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39. POS1237 ALGORITHM IDENTIFYING CHRONIC INFLAMMATORY DISEASES TREATED BY BIOTHERAPY AND/OR TARGETED SYNTHETIC TREATMENTS IN OUTPATIENT CARE IN FRANCE: FEASIBILITY, PRELIMINARY RESULTS, AND IMPACT OF COVID-19

Author: Vincent Descamps, L. Perra, Simon Pilet, Pascal Richette, Milka Maravic, and Matthieu Allez
Subjects: medicine.drug_class, business.industry, Immunology, Azathioprine, Pharmacy, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Psoriatic arthritis, Rheumatology, Ambulatory care, Psoriasis, Rheumatoid arthritis, medicine, Immunology and Allergy, Corticosteroid, Methotrexate, business, Algorithm, medicine.drug
Abstract: Background:Discriminating chronic inflammatory diseases under biotherapy and/or targeted synthetic treatments (B/TST) using medico-administrative databases are challenging but required for medico-economic analyses focusing on these diseases.Objectives:The objective was to evaluate the feasibility of using a medication dispense data in order to identify patients with chronic inflammatory diseases under B/TST in outpatient care setting and evaluate the impact of COVID-19 in FranceMethods:LRx contains all anonymized medication dispenses prescribed in outpatient care in a representative panel of French retails pharmacies, including data of near 40 million patients. Patients having at least one B/TST delivered in 2019 were selected. An algorithm was constructed using different steps, including a machine learning step by transfer learning applied in patient classified as having a rheumatologic condition in order to differentiate rheumatoid arthritis (RA) from spondyloarthritis (SA). We numbered 190,640 patients, of which 87.8% were classified in one of the following diseases: RA, SA, psoriatic arthritis (PA), psoriasis, inflammatory bowel diseases (IBD) (extrapolated data to France). Descriptive analysis was performed. The impact of COVID-19 on biotherapy initiation was evaluated during the lockdown period (W2-W19 2020) in these different conditions.Results:Among the 167,468 patients under B/TST, 20.7%, 18.4%, 6.5%, 37.9% and 16.5% were considered as having a psoriasis, IBD, PA, RA, and SA, respectively. Female patients were more frequent in RA and PA (> 60%); younger (< 20 years) and older patients (74 years) were found in patients with IBD (5.7%) and RA (12.6%), respectively. Contrasting with IBD, SA, and RA patients were mainly under anti-TNF treatment (> 90% for IBD and SA, 73.5% for RA), psoriasis and PA patients received a range of broadly well-balanced of B/TST. Among the immunosuppressant, methotrexate was mostly prescribed in RA (58.4%), PA (34.1%), and psoriasis (14.1%), and azathioprine in IBD (19.9%). Oral corticosteroid delivered at least 4 times in 2019 were mostly found to be associated with a RA condition (28%). A significant decrease of biotherapy initiation was observed during the lockdown in France in patients with IBD (-20%, p=0.03) and psoriasis (-54%, pConclusion:The algorithm was able to identify patients with chronic inflammatory diseases under B/TST delivered in outpatient care and will allow to follow-up its management and study the COVID-19 impact on biotherapy initiation. An external validation needs to be performedDisclosure of Interests:None declared
Published: 2021
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40. Sa554 CHRONIC POUCHITIS AND CROHN'S DISEASE OF THE POUCH AFTER ILEAL POUCH-ANAL ANASTOMOSIS : INCIDENCE AND RISK FACTORS

Author: Franck Carbonnel, Yoram Bouhnik, Antoine Meyer, Yves Panis, Antoine Brouquet, Nicola de’Angelis, Julien Kirchgesner, Clément Bresteau, Jérémie H. Lefevre, Matthieu Allez, Laurent Beaugerie, and Aurelien Amiot
Subjects: medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Incidence (epidemiology), Gastroenterology, medicine.disease, Ileal Pouch Anal Anastomosis, Chronic pouchitis, Internal medicine, medicine, Pouch, business
Published: 2021
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41. Duration of combination therapy and risk of treatment failure in patients with inflammatory bowel disease

Author: Matthieu Allez, Thibaut Vaysse, Antoine Rachas, Uri Kopylov, Yehuda Chowers, Bella Ungar, Elsa Lambrescak, Xavier Roblin, Aude Gleizes, Salima Hacein-Bey, and Franck Carbonnel
Subjects: Adult, Male, medicine.medical_specialty, Combination therapy, Lower risk, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, Internal medicine, Humans, Immunologic Factors, Medicine, Treatment Failure, Retrospective Studies, Hepatology, Thiopurine methyltransferase, biology, business.industry, Hazard ratio, Gastroenterology, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Infliximab, Discontinuation, Treatment Outcome, 030220 oncology & carcinogenesis, biology.protein, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, medicine.drug
Abstract: Summary Background Patients who receive infliximab (IFX) combined with a thiopurine, for inflammatory bowel disease, have a better clinical response and less frequent immunization towards IFX than those treated with IFX alone. The benefits of combination therapy must be weighed against the risks of infection and cancer. We studied the association between the duration of combination therapy and the risk of treatment failure by two year from initiation. Methods Participants had Crohn's disease or ulcerative colitis and were in clinical and biological remission, 6 months after initiation of combination therapy. The risk of subsequent treatment failure (i.e., undetectable trough IFX levels and/or clinical relapse followed by surgical treatment or switch of maintenance treatment) was estimated using Kaplan–Meier method and adjusted Hazard Ratios (aHRs), in patients whohadreceived 6 to 11 months vs. 12 months or more of combination therapy. We performed a similar analysis in which the follow-up was started at discontinuation of the immunosuppressant. Results Among 139 patients (48% women; median age 31.1), with a median follow-up of 18.9 months, we observed 26 treatment failures (including 15 patients with undetectable trough IFX levels). After adjustment for gender and type of immunomodulator, a shorter duration of combination therapy was not associated with a higher risk of treatment failure (aHR = 0.42; 95% confidence interval (95%CI): 0.13–1.40; p = 0.16). When the follow-up was started at discontinuation of the immunosuppressant, a combination therapy of 6–11 months was associated with a numerically lower risk of treatment failure as compared with a longer combination therapy (HR = 0.12; 95%CI: 0.01–1.05; p = 0.055). Conclusion Our results do not show any benefit for continuation of combination therapy for more than 12 months after achieving clinical remission in IBD patients.
Published: 2021
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42. Postoperative Complications after Ileocecal Resection in Crohn’s Disease: A Prospective Study From the REMIND Group

Author: Benjamin Pariente, Claire Auzolle, Philippe Zerbib, Anne Dubois, Yves Panis, Philippe Marteau, Jérôme Filippi, Eddy Cotte, Mathurin Fumery, Nicolas Munoz-Bongrand, Jean-Marc Gornet, Philippe Seksik, Xavier Treton, Pascal Houzé, Gilles Boschetti, Matthieu Allez, Charles Sabbagh, Carmen Stefanescu, Karine Pautrat, Marc Chevrier, Anthony Buisson, Xavier Jouven, Najim Chafai, Département de Gastroentérologie, Hôpital Européen [Fondation Ambroise Paré - Marseille], Laboratoire d'Analyses Médicales, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Department of Gastroenterological Surgery, Hop St Louis, Hospices Civils de Lyon (HCL), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Départment de Gastroentérologie, Université de Lille, Droit et Santé, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department Colorectal Surgery, Department of Gastroenterological Surgery and Transplantation, Université Lille Nord de France (COMUE), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department Digestion and Oncology Surgery, Université de Picardie Jules Verne (UPJV), Département de Gastroentérogie et Clinique Nutrition, Université de Nice Sophia-Antipolis (UNSA), CHU Trousseau [APHP], Department Gastroenteroly IBD and Nutrition Support, Association Francois Aupetit, MSD France, Helmsley Charitable Trust, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Universitaire Estaing, Department Digestion Surgery, Hopital Saint Antoine, Hôpital Lariboisière, Biochimie, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP]
Subjects: medicine.medical_specialty, medicine.medical_treatment, chirurgie, 03 medical and health sciences, Ileostomy, 0302 clinical medicine, intestin, Interquartile range, medicine, Risk factor, Prospective cohort study, intestine, maladie inflammatoire, Crohn's disease, Hepatology, business.industry, Gastroenterology, Postoperative complication, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, maladie de crohn, Odds ratio, crohn disease, medicine.disease, inflammatory disease, 3. Good health, Surgery, facteur de risque, risk factor, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, thérapie, Cohort study
Abstract: OBJECTIVES: We sought to determine the frequency of and risk factors for early (30-day) postoperative complications after ileocecal resection in a well-characterized, prospective cohort of Crohn's disease patients. METHODS: The REMIND group performed a nationwide study in 9 French university medical centers. Clinical-, biological-, surgical-, and treatment-related data on the 3 months before surgery were collected prospectively. Patients operated on between 1 September 2010 and 30 August 2014 were included. RESULTS: A total of 209 patients were included. The indication for ileocecal resection was stricturing disease in 109 (52%) cases, penetrating complications in 88 (42%), and medication-refractory inflammatory disease in 12 (6%). A two-stage procedure was performed in 33 (16%) patients. There were no postoperative deaths. Forty-three (21%) patients (23% of the patients with a one-stage procedure vs. 9% of those with a two-stage procedure, P=0.28) experienced a total of 54 early postoperative complications after a median time interval of 5 days (interquartile range, 4-12): intra-abdominal septic complications (n=38), extraintestinal infections (n=10), and hemorrhage (n=6). Eighteen complications (33%) were severe (Dindo-Clavien III-IV). Reoperation was necessary in 14 (7%) patients, and secondary stomy was performed in 8 (4.5%). In a multivariate analysis, corticosteroid treatment in the 4 weeks before surgery was significantly associated with an elevated postoperative complication rate (odds ratio (95% confidence interval)=2.69 (1.15-6.29); P=0.022). Neither preoperative exposure to anti-tumor necrosis factor (TNF) agents (n=93, 44%) nor trough serum anti-TNF levels were significant risk factors for postoperative complications. CONCLUSIONS: In this large, nationwide, prospective cohort, postoperative complications were observed after 21% of the ileocecal resections. Corticosteroid treatment in the 4 weeks before surgery was significantly associated with an elevated postoperative complication rate. In contrast, preoperative anti-TNF therapy (regardless of the serum level or the time interval between last administration and surgery) was not associated with an elevated risk of postoperative complications.
Published: 2017
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43. Diffusion-weighted MRI in Crohn's disease: Current status and recommendations

Author: Matthieu Allez, Philippe Soyer, Stuart A. Taylor, Céline Savoye-Collet, Christine Hoeffel, Anthony Dohan, Magaly Zappa, Caroline Reinhold, Mourad Boudiaf, Raphael Dautry, Xavier Dray, and Maximilien Barret
Subjects: medicine.medical_specialty, Crohn's disease, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Disease, medicine.disease, Inflammatory bowel disease, 3. Good health, 030218 nuclear medicine & medical imaging, Clinical Practice, 03 medical and health sciences, 0302 clinical medicine, medicine, Biomarker (medicine), Effective diffusion coefficient, 030211 gastroenterology & hepatology, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Radiology, business, Diffusion MRI
Abstract: Over the past years, technological improvements and refinements in magnetic resonance imaging (MRI) hardware have made high-quality diffusion-weighted imaging (DWI) routinely possible for the bowel. DWI is promising for the detection and characterization of lesions in Crohn's disease (CD) and has been advocated as an alternative to intravenous gadolinium-based contrast agents. Furthermore, quantification using the apparent diffusion coefficient may have value as a biomarker of CD activity and has shown promise. In this article we critically review the literature pertaining to the value of DWI in CD for detection, characterization, and quantification of disease activity and complications. Although the body of supportive evidence is growing, it is clear that well-designed, multicenter studies are required before the role of DWI in clinical practice can be fully established. J. Magn. Reson. Imaging 2016;44:1381-1396.
Published: 2016
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44. Anti-PD1-induced collagenous colitis in a melanoma patient

Author: Martine Bagot, Barouyr Baroudjian, Céleste Lebbé, Nelson Lourenco, Marianne Maillet, Philippe Bertheau, Matthieu Allez, Cécile Pagès, Ichrak Chami, and Jean-Marc Gornet
Subjects: Budesonide, Cancer Research, medicine.medical_specialty, Skin Neoplasms, medicine.medical_treatment, Colitis, Collagenous, Programmed Cell Death 1 Receptor, Ipilimumab, Dermatology, Pembrolizumab, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Colitis, Melanoma, Protein Kinase Inhibitors, Aged, Collagenous colitis, business.industry, Immunotherapy, medicine.disease, Regimen, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract: Targeted immunotherapy has markedly improved the survival of melanoma patients. We report the case of a melanoma patient who developed a collagenous colitis under an anti-PD1 regimen. A 68-year-old woman was treated for a stage IV melanoma. An anti-PD1, pembrolizumab, was introduced after the failure of a first-line therapy with an anti-CTLA4. At cycle 14, pembrolizumab was interrupted because of grade 3 diarrhea. Histologic analysis of colon mucosa showed a thickened apical subepithelial collagen layer with irregular collagen deposition of more than 25 µm thickness. Budesonide 9 mg/day and cholestyramin 8 g/day were then introduced, leading to a decrease in the number of stools to grade 2. Because of the prognosis of the disease, the efficacy of pembrolizumab in this patient and the lack of other efficient treatments, pembrolizumab was restarted, with no worsening of the diarrhea after a follow-up of 8 weeks. In the era of immunotherapy, a new type of drug-induced colitis has emerged because of monoclonal antibodies targeting immune checkpoints such as CTLA-4 and PD1. Gastrointestinal tract immune-mediated adverse effects are now well described with ipilimumab. To the best of our knowledge, this is the first report of a collagenous colitis in a patient treated with pembrolizumab, thus suggesting a new mechanism of toxicity. Classically, collagenous colitis first-line treatment is based on discontinuation of the suspected treatment. However, there may be a strong benefit to maintaining an anti-PD1 regimen in our patients. In this case, symptomatic management associated with budesonide and cholestyramin enabled continuation of pembrolizumab.
Published: 2016
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45. Interobserver Variation Study of the Rutgeerts Score to Assess Endoscopic Recurrence after Surgery for Crohn’s Disease

Author: Bernard Duclos, Jacques Moreau, David Laharie, Laurence Martin, Matthieu Allez, Philippe Marteau, Edouard Louis, Jean Louis Dupas, Hugues Coevoet, Guillaume Cadiot, Franck Carbonnel, Jean-Frederic Colombel, Benoit Coffin, Jean-Yves Mary, Arnaud Bourreille, and Yoram Bouhnik
Subjects: Adult, Male, medicine.medical_specialty, Colon, Video Recording, Aftercare, Anastomosis, Endoscopy, Gastrointestinal, Resection, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Ileum, Recurrence, Ileocolonic anastomosis, Health Status Indicators, Humans, Medicine, Colectomy, Observer Variation, Crohn's disease, medicine.diagnostic_test, business.industry, Anastomosis, Surgical, Gastroenterology, Reproducibility of Results, General Medicine, medicine.disease, Confidence interval, Surgery, Endoscopy, 030220 oncology & carcinogenesis, Interobserver Variation, Female, 030211 gastroenterology & hepatology, business, Kappa, Follow-Up Studies
Abstract: After resection surgery for Crohn's disease, recurrence of endoscopic lesions at the site of the anastomosis or in the neoterminal ileum is graded according to the Rutgeerts score (RS). The goal of this study was to test the interobserver variability for RS.Thirteen trained endoscopists evaluated the RS on 39 videotapes of patients who had undergone resection for Crohn's disease with an ileocolonic anastomosis 6 months earlier. Videotapes were randomly assigned to endoscopists through a balanced incomplete block design. Each videotape was scored independently by four endoscopists, and each endoscopist evaluated 12 videotapes, making a total of 156 videotape assessments. Reproducibility levels of the RS were assessed through unweighted kappa estimates among multiple raters. The proportion of inappropriate therapeutic initiation was estimated by randomly selecting one endoscopist for each videorecording, assuming that the majority of endoscopists correctly classified endoscopic recurrence.The kappa estimates were 0.43 (95% confidence interval: 0.33-0.52) for the RS on a 5-grade scale, 0.47 (0.28-0.66) for RSi2 vs. ≥ i2, and 0.64 (0.42-0.85) for RS ≤ i2 vs.i2. The percentages of inappropriate therapeutic initiation were 12.8% (3.8-21.9) when initiation was triggered by a RS ≥ i2 and 8.3% (1.1-15.6) when initiation was triggered by a RSi2 (p = 0.41).The reproducibility of the RS was moderate, especially when differentiatingi2 from ≥i2, which may lead to incorrect therapeutic decisions in10% of patients.
Published: 2016
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46. Management of Patients With Crohn's Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting

Author: Britta Siegmund, Severine Vermeire, Michael A. Kamm, Siew C. Ng, Anders Ekbom, Edouard Louis, Erica J. Brenner, Flavio Steinwurz, Miguel Regueiro, Julián Panés, David B. Sachar, Marla Dubinsky, Joel R. Rosh, David T. Rubin, Stefan Schreiber, Charles N. Bernstein, Ryan C. Ungaro, Miquel A. Gassull, Fernando Magro, James O. Lindsay, Charlie W. Lees, Edward V. Loftus, Noam Harpaz, Laurent Peyrin-Biroulet, Iris Dotan, Zhihua Ran, R. Balfour Sartor, Vineet Ahuja, Arie Levine, William J. Sandborn, Jonathan Braun, Ioannis E. Koutroubakis, Maria T. Abreu, Dan Turner, Peter D.R. Higgins, André D'Hoore, Silvio Danese, Peter L. Lakatos, Colm O'Morain, Matthieu Allez, James D. Lewis, Geert R. D'Haens, Anne M. Griffiths, Milan Lukas, Chris M. Griffiths, Jürgen Schölmerich, Pia Munkholm, Victoria Rai, Phillip Fleshner, Johan D. Söderholm, Markus F. Neurath, Michael D. Kappelman, Yehuda Chowers, Uma Mahadevan, Ashwin N. Ananthakrishnan, Eduard F. Stange, Axel Dignass, Morten H. Vatn, Mark S. Silverberg, Subrata Ghosh, Cosimo Prantera, Corey A. Siegel, Jean-Frederic Colombel, Ailsa Hart, Jonas Halfvarson, Remo Panaccione, Walter Reinisch, Gerasimos J. Mantzaris, Feza H. Remzi, Britt Christensen, Stephen B. Hanauer, Gil Kaplan, Ferdinando D'Amico, Richard B. Gearry, Dermot P.B. McGovern, Bjørn Moum, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Crohn's disease, medicine.medical_specialty, Hepatology, biology, business.industry, medicine.medical_treatment, Gastroenterology, Immunotherapy, medicine.disease, biology.organism_classification, Ulcerative colitis, digestive system diseases, Pneumonia, Internal medicine, Pandemic, medicine, Disease management (health), Colitis, business, Betacoronavirus
Abstract: The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers.
Published: 2020
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47. 946 DEEP REMISSION AT 1 YEAR IS NOT ASSOCIATED WITH BETTER OUTCOME IN CROHN'S DISEASE: LONG-TERM DATA FROM TAILORIX

Author: Severine Vermeire, Nicolas Duveau, Edouard Louis, Jérôme Filippi, David Laharie, Anthony Buisson, Peter Bossuyt, Christien J. van der Woude, Guy Lambrecht, Geert R. D'Haens, Alexandre Aubourg, Yoram Bouhnik, Filip Baert, Hedia Brixi, Matthieu Allez, Benjamin Pariente, Laurent Peyrin-Biroulet, Cyrielle Giletta, and Philippe Van Hootegem
Subjects: Crohn's disease, Pediatrics, medicine.medical_specialty, Hepatology, business.industry, Long term data, Gastroenterology, medicine, medicine.disease, business, Outcome (game theory)
Published: 2020
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48. The role of integrins in the pathogenesis of inflammatory bowel disease: Approved and investigational anti-integrin therapies

Author: Silvio Danese, Mary E. Keir, Matthieu Allez, Jacqueline McBride, Iris Dotan, Swati Tole, Dotan, Iri, Allez, Matthieu, Danese, Silvio, Keir, Mary, Tole, Swati, and Mcbride, Jacqueline
Subjects: Integrins, T-Lymphocytes, Integrin, Inflammation, Review Article, Inflammatory bowel disease, digestive system, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, anti‐integrin therapy, inflammatory bowel disease, Drug Discovery, Medicine, Animals, Humans, Molecular Targeted Therapy, Lymphocyte homing receptor, Review Articles, 030304 developmental biology, ulcerative colitis, Pharmacology, 0303 health sciences, Gastrointestinal tract, biology, business.industry, Cell adhesion molecule, Drugs, Investigational, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, Gastrointestinal Tract, Crohn's disease, 030220 oncology & carcinogenesis, anti-integrin therapy, Immunology, biology.protein, integrins, Molecular Medicine, medicine.symptom, Crohn's disease, ulcerative colitis, business
Abstract: Inflammatory bowel disease (IBD) is characterized by uncontrolled inflammation in the gastrointestinal tract. The underlying pathobiology of IBD includes an increase in infiltrating gut‐homing lymphocytes. Although lymphocyte homing is typically a tightly regulated and stepwise process involving multiple integrins and adhesion molecules expressed on endothelial cells, the distinct roles of integrin‐expressing immune cells is not fully understood in the pathology of IBD. In this review, we detail the involvement of integrins expressed on specific lymphocyte subsets in the pathogenesis of IBD and discuss the current status of approved and investigational integrin‐targeted therapies.
Published: 2019

49. Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus

Author: Matthieu Allez, Silvio Danese, Severine Vermeire, Ailsa Hart, Stephan R. Vavricka, Javier P. Gisbert, Stefan Schreiber, Ad A. van Bodegraven, Fernando Magro, Laurent Peyrin-Biroulet, Jonas Halfvarson, Peter L. Lakatos, Iris Dotan, Dino Tarabar, Danese, S, Allez, M, van Bodegraven, Aa, Dotan, I, Gisbert, Jp, Hart, A, Lakatos, Pl, Magro, F, Peyrin-Biroulet, L, Schreiber, S, Tarabar, D, Vavricka, S, Halfvarson, J, Vermeire, S, University of Zurich, and Vermeire, Séverine
Subjects: medicine.medical_specialty, MAINTENANCE THERAPY, Consensus, Delphi method, 610 Medicine & health, Disease, Cochrane Library, DECISION-MAKING, Unmet needs, 03 medical and health sciences, 0302 clinical medicine, NECROSIS FACTOR-ALPHA, QUALITY-OF-LIFE, Surveys and Questionnaires, Medicine, Humans, In patient, 2715 Gastroenterology, Practice Patterns, Physicians', Health Services Needs and Demand, Science & Technology, Gastroenterology & Hepatology, Consensus panel, business.industry, Systematic literature review, Gastroenterology, CLINICAL-RESPONSE, General Medicine, ANTI-TNF THERAPY, medicine.disease, Expert group, Ulcerative colitis, CROHNS-DISEASE, COMBINATION THERAPY, Systematic review, 10219 Clinic for Gastroenterology and Hepatology, 030220 oncology & carcinogenesis, Family medicine, RISK-FACTORS, 030211 gastroenterology & hepatology, Delphi process, Colitis, Ulcerative, business, Life Sciences & Biomedicine, INFLAMMATORY-BOWEL-DISEASE
Abstract: Background: The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC. Methods: PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings. Results: In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients’ daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs. Conclusions: These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC.
Published: 2019

50. Crohn's Disease Mucosal Transcriptomes Highlight JAK/STAT Pathway Involvement in Postoperative Recurrence

Author: Marjolaine Ngollo, Kevin Perez, Nassim Hammoudi, Yuri Gorelik, Marc Delord, Claire Auzolle, Hugo Bottois, Dominique Cazals-Hatem, Madeleine Bezault, Stéphane Nancey, Benjamin Pariente, Xavier Treton, Mathurin Fumery, Antony Buisson, Nicolas Barnich, Philippe Seksik, REMIND Study Group Invertigators, Shai S. Shen-Orr, Lionel Le Bourhis, and Matthieu Allez
Subjects: medicine.medical_specialty, Crohn's disease, business.industry, JAK-STAT signaling pathway, medicine.disease, Gastroenterology, Ileal resection, Resection, Internal medicine, medicine, Clinical endpoint, Intestinal resection, Prospective cohort study, business, Trial registration
Abstract: Background: Crohn's disease displays heterogeneity in terms of disease location, progression and response to treatment. Most patients require an intestinal resection due to complicated disease, and a majority of them will experience disease recurrence. We aimed to characterize biological pathways driving postoperative recurrence and to identify predictors which could guide therapeutic management. Methods: In this multicentre prospective study, we conducted transcriptome analysis on ileal mucosa of CD patients undergoing ileocolonic resection. Samples were collected from the most inflamed part of the ileum (n=200), from the ileal resection margin (n=149) and in the neo-terminal ileum 6 months after surgery (n=122). The primary endpoint was postoperative endoscopic recurrence at month 6. We applied a regression model to identify gene signatures predicting for endoscopic recurrence. Findings: Molecular patterns of early endoscopic recurrence significantly differed from those observed in chronic inflammation. Gene expression analysis of the inflamed area of the surgical specimens identified clusters of CD patients. However, pathway gene signatures at the ileal margin were superior to those of the inflamed area to predict postoperative outcome. Several pathways, including JAK/STAT signalling, cell adhesion molecules and extracellular matrix protein were associated with a higher risk of endoscopic recurrence. JAK/STAT pathway activation at the ileal margin predicted early postoperative endoscopic recurrence (AUC of 0*74) and was associated with a higher of clinical relapse on the long term. A significant increase of p-STAT3 levels at the ileal margin was associated with severe endoscopic recurrence (i3, i4) compared to no recurrence (i0) (p=0*02) and moderate recurrence (i1, i2) (p=0*04). Interpretation: Gene expression analysis at the ileal margin of the surgical specimen may strongly predict postoperative outcome. The inflammatory processes associated with postoperative recurrence differ from those engaged in chronic inflammation. Activation of JAK/STAT signalling at the ileal margin of the surgical specimen is predictive of postoperative recurrence and should be specifically targeted. Trial Registration: ClinicalTrials.gov (NCT03458195). Funding Statement: This work was supported by Helmsley Charitable Trust and the Institut national de sante et de la recherche biomedical (INSERM). Declaration of Interests: SN received honoraria from MSD, Abbvie, Takeda, Janssen, HAC Pharma, Tillots, Ferring, and Novartis. BP received honoraria from AbbVie, MSD, Takeda, Janssen, Bioagaran, and Ferring. AB received honoraria from MSD, Abbvie, Ferring, Takeda, Vifor Pharma, Sanofi-Aventis, Hospira, and Janssen. XT received honoraria from Abbvie, MSD, Takeda, Ferring, Norgine, and Janssen. MF received honoraria from AbbVie, MSD, Takeda, Janssen, Pfizer, Ferring, and Boehringer. PS received honoraria from Takeda, MSD, Biocodex, Ferring and Abbvie and financial support from Takeda. MA received honoraria from Janssen, Takeda, Pfizer, MSD, Abbvie, Ferring, Amgen, Biogen, Celgene, and Genentech/Roche. All other authors have no conflict of interest regarding this study. Ethics Approval Statement: All patients provided an informed written consent. The study was approved by AFFSAPS (IDRCB: 2009-A00205-52) and the French Ethic Committee (CPP 2009/17).
Published: 2019
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