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1. Magnetic Resonance Enterography Assessment of Transmural Healing with Vedolizumab in Moderate to Severe Crohn’s Disease: Feasibility in the VERSIFY Phase 3 Clinical Trial

Author

Rimola J, Colombel JF, Bressler B, Adsul S, Siegelman J, Cole PE, Lindner D, and Danese S

Subjects
vedolizumab, magnetic resonance enterography, crohn’s disease, clinical trials, imaging, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Jordi Rimola,1 Jean-Frédéric Colombel,2 Brian Bressler,3 Shashi Adsul,4 Jenifer Siegelman,5 Patricia E Cole,5 Dirk Lindner,4 Silvio Danese6 1IBD Unit, Radiology Department, Hospital Clínic de Barcelona, Barcelona, Spain; 2The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada; 4Takeda Pharmaceuticals International, Zurich, Switzerland; 5Takeda Pharmaceuticals International, Cambridge, MA, USA; 6Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, ItalyCorrespondence: Jordi Rimola, IBD Unit, Radiology Department, Hospital Clínic de Barcelona, Barcelona, Spain, Tel +34 932 275 400, Email jrimola@clinic.catPurpose: The VERSIFY phase 3 trial in patients with Crohn’s disease (CD) treated with vedolizumab was the first to include a substudy that used a standardized magnetic resonance enterography (MRE) protocol to assess features of transmural inflammation (bowel edema and wall thickness) and extramural disease activity (enlarged lymph nodes).Patients and Methods: Patients received intravenous vedolizumab (300 mg) at weeks 0 (baseline), 2, and 6, and then every 8 weeks for 26 or 52 weeks. Post hoc analyses included a subpopulation with a Magnetic Resonance Index of Activity score of ≥ 7 in at least one bowel segment at baseline and at least one postbaseline MRE assessment. Changes in transmural inflammation, including intramural bowel edema and wall thickness, were evaluated. Patient-level and segment-level analyses were performed.Results: MRE images were evaluated in 27 patients with 83 evaluable bowel segments at baseline and week 26, and 13 patients with 38 evaluable segments at baseline, week 26, and week 52. At baseline, all patients had bowel wall edema and wall thickness of > 3 mm in at least one bowel segment. The proportion of patients with edema decreased at weeks 26 (17/27 [63.0%]) and 52 (4/13 [30.8%]) and the proportion with bowel wall thickness of > 3 mm decreased at weeks 26 (25/27 [92.6%]) and 52 (10/13 [76.9%]).Conclusion: In patients with CD treated with vedolizumab for 26 and 52 weeks, the number of patients, and bowel segments, with MRE-detected transmural inflammation was reduced. These results highlight the impact of vedolizumab on components of transmural inflammation in CD and demonstrate that using MRE in CD multicenter clinical trials is feasible.Trial Registration: ClinicalTrials.gov NCT02425111, April 23, 2015, http://www.clinicaltrials.gov NCT02425111; EU Clinical Trials Register EudraCT 2014– 003509-13, https://www.clinicaltrialsregister.eu. Keywords: vedolizumab, magnetic resonance enterography, Crohn’s disease, clinical trials, imaging

Published
2024

2. Sustained Corticosteroid-Free Clinical Remission During Vedolizumab Maintenance Therapy in Patients with Ulcerative Colitis on Stable Concomitant Corticosteroids During Induction Therapy: A Post Hoc Analysis of GEMINI 1

Author

Loftus EV Jr, Sands BE, Colombel JF, Dotan I, Khalid JM, Tudor D, and Geransar P

Subjects
vedolizumab, ulcerative colitis, corticosteroid, anti-tumor necrosis factor alpha, clinical remission, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Edward V Loftus Jr,1 Bruce E Sands,2 Jean-Frédéric Colombel,2 Iris Dotan,3 Javaria Mona Khalid,4 David Tudor,5 Parnia Geransar5 1Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA; 2The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA; 3Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 4Takeda International – UK Branch, London, UK; 5Takeda Pharmaceuticals International AG, Zurich, SwitzerlandCorrespondence: Edward V Loftus JrDivision of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USATel +1-507-284-2511Email loftus.edward@mayo.eduBackground: Corticosteroid-free clinical remission is important in ulcerative colitis.Objective: This GEMINI 1 post hoc analysis evaluated vedolizumab efficacy in achieving sustained corticosteroid-free clinical remission in moderately to severely active ulcerative colitis.Materials and Methods: GEMINI 1 included a 6-week induction period followed by a 46-week maintenance period. Patients received stable corticosteroid dosing at baseline/during induction and tapered dosing during maintenance. Analysis groups included vedolizumab (induction and maintenance); vedolizumab/placebo (vedolizumab induction, placebo maintenance); and placebo (induction and maintenance). The primary endpoint was sustained corticosteroid-free clinical remission (partial Mayo score ≤ 2, no individual subscore > 1, for ≥ 32 weeks). Multivariate analyses identified covariates associated with the primary endpoint. Safety endpoints included adverse events.Results: Baseline demographics and concomitant corticosteroid use were similar across groups (n=454). A greater proportion (95% confidence interval) of the vedolizumab group achieved sustained corticosteroid-free clinical remission (10.2% [6.9 to 13.6]) vs the placebo group (1.4% [0.0 to 7.3]; difference 8.9% [– 3.8 to 21.4]). Proportions were similar between the vedolizumab/placebo and placebo groups. Covariates associated with sustained corticosteroid-free clinical remission (odds ratio [95% confidence interval]) were treatment (vedolizumab vs placebo: 9.35 [1.25 to 71.43]; p=0.0605), anti-tumor necrosis factor alpha exposure (yes vs no: 0.26 [0.12 to 0.57]; p=0.0008), and disease duration (≤ 2 vs > 2 years: 2.66 [0.99– 7.19]; p=0.0531). Adverse events were similar across groups.Conclusion: A numerically greater proportion of vedolizumab-treated patients with ulcerative colitis achieved sustained corticosteroid-free clinical remission. Vedolizumab treatment, no previous anti-tumor necrosis factor alpha exposure, and shorter disease duration were associated with sustained corticosteroid-free clinical remission.Clinicaltrials.gov: NCT00783718.Keywords: vedolizumab, ulcerative colitis, corticosteroid, anti-tumor necrosis factor alpha, clinical remission

Published
2020

3. Antibody responses to SARS-CoV-2 vaccination outperform responses induced by natural infection in patients with IBD receiving immunosuppressive medications: a report from the ICARUS-IBD consortium

Author

Cueto, E Gonzalez, Matthew, E, Wellens, J, Pazos, V Martinez, Thompson, C, Klenerman, P, Cadwell, K, Colombel, JF, Satsangi, J, and Wong, SY

Subjects
Science & Technology, Gastroenterology & Hepatology, Life Sciences & Biomedicine
Abstract

ispartof: pages:I228-I230 ispartof: JOURNAL OF CROHNS & COLITIS vol:17 pages:I228-I230 status: published

Published
2023

4. Measuring patients’ satisfaction with their anti-TNF treatment in severe Crohn’s disease: scoring and psychometric validation of the Satisfaction for PAtients in Crohn’s diseasE Questionnaire (SPACE-Q©)

Author

Gilet H, Arnould B, Fofana F, Clerson P, Colombel JF, D'Hondt O, Faure P, Hagège H, Nachury M, Nahon S, Tucat G, Vandromme L, Cazala-Telinge I, and Thibout E

Subjects
Medicine (General), R5-920
Abstract

Hélène Gilet,1 Benoit Arnould,1 Fatoumata Fofana,1 Pierre Clerson,2 Jean-Frédéric Colombel,10 Olivier D’Hondt,2 Patrick Faure,4 Hervé Hagège,5 Maria Nachury,3 Stéphane Nahon,6 Gilbert Tucat,7 Luc Vandromme,8 Ines Cazala-Telinge,9 Emmanuel Thibout9 1HEOR and Strategic Market Access, Mapi, Lyon, France; 2Orgamétrie, Roubaix, France; 3Hôpital Claude Huriez, Lille, France; 4Clinique Saint-Jean du Languedoc, Toulouse, France; 5Centre Hospitalier Intercommunal, Créteil, France; 6Centre Hospitalier Intercommunal, Le Raincy Montfermeil, France; 7Gastroenterologist, Private Clinical Practice, Paris, France; 8Gastroenterologist, Private Clinical Practice, Reims, France; 9Abbvie France, Rungis, France; 10Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Severe Crohn’s disease management includes anti-tumor necrosis factor (anti-TNF) drugs that differ from early-stage treatments regarding efficacy, safety, and convenience. This study aimed to finalize and psychometrically validate the Satisfaction for PAtients in Crohn’s diseasE Questionnaire (SPACE-Q©), developed to measure satisfaction with anti-TNF treatment in patients with severe Crohn’s disease. Methods: A total of 279 patients with severe Crohn’s disease receiving anti-TNF therapy completed the SPACE-Q 62-item pilot version at inclusion and 12 and 13 weeks after first anti-TNF injection. The final SPACE-Q scoring was defined using multitrait and regression analyses and clinical relevance considerations. Psychometric validation included clinical validity against Harvey–Bradshaw score, concurrent validity against Treatment Satisfaction Questionnaire for Medication (TSQM), internal consistency reliability, test–retest reliability, and responsiveness against the patient global impression of change (PGIC).Results: Quality of completion was good (55%–67% of patients completed all items). Four items were removed from the questionnaire. Eleven scores were defined within the final 58-item SPACE-Q: disease control; symptoms, anal symptoms, and quality of life transition scales; tolerability; convenience; expectation confirmation toward efficacy, side effects, and convenience; satisfaction with treatment; and motivation. Scores met standards for concurrent validity (correlation between SPACE-Q satisfaction with treatment and TSQM satisfaction scores =0.59), internal consistency reliability (Cronbach’s α=0.67–0.93), test–retest reliability (intraclass correlations =0.62–0.91), and responsiveness (improvement in treatment experience assessed by the SPACE-Q for patients reporting improvement on the PGIC). Significantly different mean scores were observed between groups of patients with different Harvey–Bradshaw disease severity scores.Conclusion: The SPACE-Q is a valid, reliable, and responsive instrument to measure satisfaction with anti-TNF treatment in patients with severe Crohn’s disease and for use in future studies. Keywords: Crohn’s disease, satisfaction, anti-TNF treatment, questionnaire

Published
2014

5. Ulcerative proctitis is a frequent location of paediatric-onset UC and not a minor disease: a population-based study

Author

Hochart, A, Gower-Rousseau, C, Sarter, H, Fumery, M, Ley, D, Spyckerelle, C, Peyrin-Biroulet, L, Laberenne, J-E, Vasseur, F, Savoye, G, Turck, D, Andre, JM, Antonietti, M, Aouakli, A, Armand, A, Aroichane, I, Assi, F, Aubet, JP, Auxenfants, E, Ayafi-Ramelot, F, Azzouzi, K, Bankovski, D, Barbry, B, Bardoux, N, Baron, P, Baudet, A, Bazin, B, Bebahani, A, Becqwort, JP, Benet, V, Benali, H, Benguigui, C, Ben Soussan, E, Bental, A, Berkelmans, I, Bernet, J, Bernou, K, Bernou-Dron, C, Bertot, P, Bertiaux-Vandaële, N, Bertrand, V, Billoud, E, Biron, N, Bismuth, B, Bleuet, M, Blondel, F, Blondin, V, Bohon, P, Boniface, E, Bonnière, P, Bonvarlet, E, Bonvarlet, P, Boruchowicz, A, Bostvironnois, R, Boualit, M, Bouche, B, Boudaillez, C, Bourgeaux, C, Bourgeois, M, Bourguet, A, Bourienne, A, Branche, J, Bray, G, Brazier, F, Breban, P, Bridenne, M, Brihier, H, Brung-Lefebvre, V, Bulois, P, Burgiere, P, Butel, J, Canva, JY, Canva-Delcambre, V, Capron, JP, Cardot, F, Carpentier, P, Cartier, E, Cassar, JF, Cassagnou, M, Castex, JF, Catala, P, Cattan, S, Catteau, S, Caujolle, B, Cayron, G, Chandelier, C, Chantre, M, Charles, J, Charneau, T, Chavance-Thelu, M, Chirita, D, Choteau, A, Claerbout, JF, Clergue, PY, Coevoet, H, Cohen, G, Collet, R, Colombel, JF, Coopman, S, Corvisart, J, Cortot, A, Couttenier, F, Crinquette, JF, Crombe, V, Dadamessi, I, Dapvril, V, Davion, T, Dautreme, S, Debas, J, Degrave, N, Dehont, F, Delatre, C, Delcenserie, R, Delette, O, Delgrange, T, Delhoustal, L, Delmotte, JS, Demmane, S, Deregnaucourt, G, Descombes, P, Desechalliers, JP, Desmet, P, Desreumaux, P, Desseaux, G, Desurmont, P, Devienne, A, Devouge, E, Devred, M, Devroux, A, Dewailly, A, Dharancy, S, Di Fiore, A, Djeddi, D, Djedir, R, Dreher-Duwat, ML, Dubois, R, Dubuque, C, Ducatillon, P, Duclay, J, Ducrocq, B, Ducrot, F, Ducrotte, P, Dufilho, A, Duhamel, C, Dujardin, D, Dumant-Forest, C, Dupas, JL, Dupont, F, Duranton, Y, Duriez, A, El Achkar, K, El Farisi, M, Elie, C, Elie-Legrand, MC, Elkhaki, A, Eoche, M, Evrard, D, Evrard, JP, Fatome, A, Filoche, B, Finet, L, Flahaut, M, Flamme, C, Foissey, D, Fournier, P, Foutrein-Comes, MC, Foutrein, P, Fremond, D, Frere, T, Gallet, P, Gamblin, C, Ganga, S, Gerard, R, Geslin, G, Gheyssens, Y, Ghossini, N, Ghrib, S, Gilbert, T, Gillet, B, Godard, D, Godard, P, Godchaux, JM, Godchaux, R, Goegebeur, G, Goria, O, Gottrand, F, Gower, P, Grandmaison, B, Groux, M, Guedon, C, Guillard, JF, Guillem, L, Guillemot, F, Guimberd, D, Haddouche, B, Hakim, S, Hanon, D, Hautefeuille, V, Heckestweiller, P, Hecquet, G, Hedde, JP, Hellal, H, Henneresse, PE, Heyman, B, Heraud, M, Herve, S, Hochain, P, Houssin-Bailly, L, Houcke, P, Huguenin, B, Iobagiu, S, Ivanovic, A, Iwanicki-Caron, I, Janicki, E, Jarry, M, Jeu, J, Joly, JP, Jonas, C, Katherin, F, Kerleveo, A, Khachfe, A, Kiriakos, A, Kiriakos, J, Klein, O, Kohut, M, Kornhauser, R, Koutsomanis, D, Laffineur, G, Lagarde, M, Lalanne, A, Lannoy, P, Lapchin, J, Laprand, M, Laude, D, Leblanc, R, Lecieux, P, Leclerc, N, Le Couteulx, C, Ledent, J, Lefebvre, J, Lefiliatre, P, Legrand, C, Le Grix, A, Lelong, P, Leluyer, B, Lenaerts, C, Lepileur, L, Leplat, A, Lepoutre-Dujardin, E, Leroi, H, Leroy, MY, Lesage, JP, Lesage, X, Lesage, J, Lescanne-Darchis, I, Lescut, J, Lescut, D, Leurent, B, Levy, P, Lhermie, M, Lion, A, Lisambert, B, Loire, F, Louf, S, Louvet, A, Luciani, M, Lucidarme, D, Lugand, J, Macaigne, O, Maetz, D, Maillard, D, Mancheron, H, Manolache, O, Marks-Brunel, AB, Marti, R, Martin, F, Martin, G, Marzloff, E, Mathurin, P, Mauillon, J, Maunoury, V, Maupas, JL, Mesnard, B, Metayer, P, Methari, L, Meurisse, B, Meurisse, F, Michaud, L, Mirmaran, X, Modaine, P, Monthe, A, Morel, L, Mortier, PE, Moulin, E, Mouterde, O, Mudry, J, Nachury, M, NʼGuyen Khac, E, Notteghem, B, Ollevier, V, Ostyn, A, Ouraghi, A, Ouvry, D, Paillot, B, Panien-Claudot, N, Paoletti, C, Papazian, A, Parent, B, Pariente, B, Paris, JC, Patrier, P, Paupart, L, Pauwels, B, Pauwels, M, Petit, R, Piat, M, Piotte, S, Plane, C, Plouvier, B, Pollet, E, Pommelet, P, Pop, D, Pordes, C, Pouchain, G, Prades, P, Prevost, A, Prevost, JC, Quesnel, B, Queuniet, AM, Quinton, JF, Rabache, A, Rabelle, P, Raclot, G, Ratajczyk, S, Rault, D, Razemon, V, Reix, N, Revillon, M, Richez, C, Robinson, P, Rodriguez, J, Roger, J, Roux, JM, Rudelli, A, Saber, A, Schlosseberg, P, Segrestin, M, Seguy, D, Serin, M, Seryer, A, Sevenet, F, Shekh, N, Silvie, J, Simon, V, Talbodec, N, Techy, A, Thelu, JL, Thevenin, A, Thiebault, H, Thomas, J, Thorel, JM, Tielman, G, Tode, M, Toisin, J, Tonnel, J, Touchais, JY, Touze, Y, Tranvouez, JL, Triplet, C, Uhlen, S, Vaillant, E, Valmage, C, Vanco, D, Vandamme, H, Vanderbecq, E, Vander Eecken, E, Vandermolen, P, Vandevenne, P, Vandeville, L, Vandewalle, A, Vandewalle, C, Vaneslander, P, Vanhoove, JP, Vanrenterghem, A, Varlet, P, Vasies, I, Verbiese, G, Vernier-Massouille, G, Vermelle, P, Verne, C, Vezilier-Cocq, P, Vigneron, B, Vincendet, M, Viot, J, Voiment, YM, Wacrenier, A, Waeghemaecker, L, Wallez, JY, Wantiez, M, Wartel, F, Weber, J, Willocquet, JL, Wizla, N, Wolschies, E, Zalar, A, Zaouri, B, Zellweger, A, and Ziade, C

Published
2017
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6. POSA250 Impact of Iron-Deficiency Anaemia on Disease Progression in Patients with Inflammatory Bowel Disease: A Real-World Data Analysis in Italy

Author

Fiorino, G, primary, Colombel, JF, additional, Katsanos, K, additional, Koutroubakis, IE, additional, Mearin, F, additional, Stein, J, additional, Andretta, M, additional, Antonacci, S, additional, Arenare, L, additional, Citraro, R, additional, Di Manno, G, additional, Perrone, V, additional, Veronesi, C, additional, Giacomini, E, additional, Alessandrini, D, additional, Cucala, M, additional, Ramirez de Arellano Serna, A, additional, and Degli Esposti, L, additional

Published
2022
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7. POSC250 Association Between Iron Therapies and Inflammatory Bowel Disease Progression in Patients with Iron Deficiency Anemia: A Retrospective Real-World Evidence Study in an Italian Setting

Author

Fiorino, G, primary, Colombel, JF, additional, Katsanos, K, additional, Koutroubakis, IE, additional, Mearin, F, additional, Stein, J, additional, Andretta, M, additional, Antonacci, S, additional, Arenare, L, additional, De, Francesco A, additional, Dell'Orco, S, additional, Perrone, V, additional, Veronesi, C, additional, Dovizio, M, additional, Blini, V, additional, Cucala, M, additional, Ramirez, de Arellano Serna A, additional, and Degli, Esposti L, additional

Published
2022
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9. Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis

Author

Paramsothy, S, Nielsen, S, Kamm, MA, Deshpande, NP, Faith, JJ, Clemente, JC, Paramsothy, R, Walsh, AJ, van den Bogaerde, J, Samuel, D, Leong, RWL, Connor, S, Ng, W, Lin, E, Borody, TJ, Wilkins, MR, Colombel, JF, Mitchell, HM, Kaakoush, NO, Paramsothy, S, Nielsen, S, Kamm, MA, Deshpande, NP, Faith, JJ, Clemente, JC, Paramsothy, R, Walsh, AJ, van den Bogaerde, J, Samuel, D, Leong, RWL, Connor, S, Ng, W, Lin, E, Borody, TJ, Wilkins, MR, Colombel, JF, Mitchell, HM, and Kaakoush, NO

Abstract

Background & Aims: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy. Methods: We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multidonor FMT or placebo enemas, 5 d/wk for 8 weeks. Patients in the FMT group received blended homogenized stool from 3–7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 large-bowel biopsy samples from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT, if applicable. We analyzed 105 fecal samples from the 14 individual donors (n = 55), who in turn contributed to 21 multidonor batches (n = 50). Bacteria in colonic and fecal samples were analyzed by both 16S ribosomal RNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics, and 60 fecal samples were analyzed for metabolome features. Results: FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared with patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans compared with patients who did not achieve remission after FMT and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had en

Published
2019

12. Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease

Author

Sandborn, Wj, Feagan, Bg, Rutgeerts, P, Hanauer, S, Colombel, Jf, Sands, Be, Lukas, M, Fedorak, Rn, Lee, S, Bressler, B, Fox, I, Rosario, M, Sankoh, S, Xu, J, Stephens, K, Milch, C, Parikh, A, Bampton P, GEMINI 2 Study G. r. o. u. p., Borody, T, Chung, A, Debinski, H, Florin, T, Hetzel, D, Jakobovits, S, Lawrance, I, Leong, R, Macrae, F, Mitchell, B, Moore, G, Pavli, P, Samuel, D, Weltman, M, Haas, T, Reinisch, W, Vogel, W, Baert, F, De Maeyer, M, De Vos, M, Dewit, O, D'Haens, G, Louis, E, Muls, V, Van Assche, G, Krastev, Z, Nikolovska, D, Petrov, P, Petrov, A, Stoinov, S, Tchernev, K, Vasileva, G, Aumais, G, Axler, J, Bailey, R, Bernstein, C, Bitton, A, Bourdages, R, Cohen, A, Devroede, G, Dhalla, S, Feagan, B, Fedorak, R, Green, D, Greenberg, G, Jones, J, Larkai, E, Macintosh, D, Panaccione, R, Ponich, T, Singh, R, Sy, R, Wiesinger, H, Albin, A, Douda, L, Horny, I, Stehlik, J, Stuksa, J, Volfova, M, Vyhnalek, P, Zadorova, Z, Andersen, V, Bendtsen, F, Fallingborg, J, Rannem, T, Maelt, A, Margus, B, Salupere, R, Allez, M, Des Varennes SB, Desreumaux, P, Dupas, Jl, Grimaud, Jc, Hebuterne, X, Lerebours, E, Picon, L, Zerbib, F, Aldinger, V, Baumgart, D, Buening, C, Dollinger, M, Hoffmann, P, Howaldt, S, Klaus, J, Konturek, Jw, Krummenerl, T, Malfertheiner, P, Schmidt, W, Schreiber, S, Seidler, U, Stallmach, A, Stremmel, W, Zeitz, M, Mantzaris, G, Triantafyllou, K, Ng, C, Bene, L, Fazekas, I, Fejes, R, Gall, J, Horvat, G, Hunyady, B, Salamon, A, Toth, T, Tulassay, Z, Varga, E, Varga, M, Varga Szabo, L, Vincze, A, Oddsson, E, Örvar, K, Ahuja, V, Amarapurkar, D, Chandra, A, Koshy, A, Krishna, P, Ramakrishna, K, Reddy, N, Thorat, V, Patchett, S, Ryan, B, Ben Horin, S, Fishman, S, Lavy, A, Rachmilewitz, D, Ardizzone, S, Corazziari, E, Danese, S, Fries, Walter, Gasbarrini, A, Kohn, A, Sturniolo, Gc, Danilans, A, George, Am, Hilmi, In, Engels, Lg, Ponsioen, Cy, van der Woude CJ, Gearry, R, Haines, M, Schultz, M, Wallace, I, Wyeth, J, Florholmen, J, Jahnsen, J, Lygren, I, Röseth, A, Ciecko Michalska, I, Gonciarz, M, Horynski, M, Huk, J, Jamrozik Kruk, Z, Janke, A, Klupinska, G, Marecik, J, Paradowski, L, Rudzinski, J, Rydzewska, G, Han, Ds, Hong, Sp, Kim, Hj, Kim, Js, Kim, Ko, Kim, Yh, Yang, Sk, Gheorghe, Ls, Voiosu, Rm, Alexeeva, O, Baranovsky, A, Bunkova, E, Burnevich, E, Dolgikh, O, Grinevich, V, Lakhin, A, Tarabar, D, Ling, Kl, Bunganic, I, Cernok, S, Gregus, M, Coetzer, T, Grundling, H, Moola, Sa, Wright, Jp, Ziady, C, Bermejo, F, Calvet, X, Herrerias, Jm, Perez Calle JL, Perez Gisbert, J, Hertervig, E, Karlen, P, Michetti, P, Rogler, G, Seibold, F, Wu, Dc, Atug, O, Kurdas, Oo, Datsenko, O, Dorofyeyev, A, Dudar, L, Golovchenko, O, Klyarits'Ka, I, Skrypnyk, I, Hawthorne, Ab, Middleton, S, Abreu, M, Bala, N, Becker, S, Behm, B, Braun, R, Bukhari, M, Chen, S, Coates, A, Dar, S, Dassopoulos, T, De Villiers, W, Desautels, S, Desta, T, Dimitroff, J, Dryden, G, Duvall, A, Farraye, F, Fein, S, Liu, Bf, Gatof, D, Geenen, D, Ginsburg, P, Glombicki, A, Glover, S, Gordon, G, Grisolano, S, Hanson, J, Hardi, R, Hoffman, B, Isaacs, K, Kim, C, Koval, G, Lashner, B, Lawitz, E, Leman, B, Levine, J, Loftus, E, Mahadevan, U, Mannon, P, Marcet, J, Matsuyama, R, Matusow, G, Mccabe, R, Mirkin, K, Murphy, M, Mushahwar, A, Mutlu, E, Nagrani, M, Nguyen, D, Nichols, M, Nieves Ramirez, A, Oubre, B, Pace, S, Pandak, W, Perera, L, Quadri, A, Quallich, L, Rajapakse, R, Randall, C, Regueiro, M, Safdi, A, Sandborn, W, Sands, B, Saubermann, L, Scherl, E, Schwartz, D, Sedghi, S, Shafran, I, Shepard, R, Siegel, C, Stein, L, Tatum, H, Triebling, A, Vasudeva, R, Winston, B, Wolf, D, Younes, Z, Jewell, D, Mahon, J, Rothstein, R, Snydman, D, Massaro, J, Clifford, D, Berger, J, Major, E, Provenzale, J, Lev, M., GEMINI 2 Study Group, Bampton, P., Borody, T., Chung, A., Debinski, H., Florin, T., Hetzel, D., Jakobovits, S., Lawrance, I., Leong, R., Macrae, F., Mitchell, B., Moore, G., Pavli, P., Samuel, D., Weltman, M., Haas, T., Reinisch, W., Vogel, W., Baert, F., De Maeyer, M., De Vos, M., Dewit, O., D'Haens, G., Louis, E., Muls, V., Van Assche, G., Krastev, Z., Nikolovska, D., Petrov, P., Petrov, A., Stoinov, S., Tchernev, K., Vasileva, G., Aumais, G., Axler, J., Bailey, R., Bernstein, C., Bitton, A., Bourdages, R., Bressler, B., Cohen, A., Devroede, G., Dhalla, S., Feagan, B., Fedorak, R., Green, D., Greenberg, G., Jones, J., Larkai, E., MacIntosh, D., Panaccione, R., Ponich, T., Singh, R., Sy, R., Wiesinger, H., Albin, A., Douda, L., Horny, I., Lukas, M., Stehlik, J., Stuksa, J., Volfova, M., Vyhnalek, P., Zadorova, Z., Andersen, V., Bendtsen, F., Fallingborg, J., Rannem, T., Maelt, A., Margus, B., Salupere, R., Allez, M., Des Varennes SB., Desreumaux, P., Dupas, JL., Grimaud, JC., Hebuterne, X., Lerebours, E., Picon, L., Zerbib, F., Aldinger, V., Baumgart, D., Buening, C., Dollinger, M., Hoffmann, P., Howaldt, S., Klaus, J., Konturek, JW., Krummenerl, T., Malfertheiner, P., Schmidt, W., Schreiber, S., Seidler, U., Stallmach, A., Stremmel, W., Zeitz, M., Mantzaris, G., Triantafyllou, K., Ng, C., Bene, L., Fazekas, I., Fejes, R., Gall, J., Horvat, G., Hunyady, B., Salamon, A., Toth, T., Tulassay, Z., Varga, E., Varga, M., Varga-Szabo, L., Vincze, A., Oddsson, E., Örvar, K., Ahuja, V., Amarapurkar, D., Chandra, A., Koshy, A., Krishna, P., Ramakrishna, K., Reddy, N., Thorat, V., Patchett, S., Ryan, B., Ben Horin, S., Fishman, S., Lavy, A., Rachmilewitz, D., Ardizzone, S., Corazziari, E., Danese, S., Fries, W., Gasbarrini, A., Kohn, A., Sturniolo, GC., Danilans, A., George, AM., Hilmi, IN., Engels, LG., Ponsioen, CY., van der Woude CJ., Gearry, R., Haines, M., Schultz, M., Wallace, I., Wyeth, J., Florholmen, J., Jahnsen, J., Lygren, I., Röseth, A., Ciecko-Michalska, I., Gonciarz, M., Horynski, M., Huk, J., Jamrozik-Kruk, Z., Janke, A., Klupinska, G., Marecik, J., Paradowski, L., Rudzinski, J., Rydzewska, G., Han, DS., Hong, SP., Kim, HJ., Kim, JS., Kim, KO., Kim, YH., Yang, SK., Gheorghe, LS., Voiosu, RM., Alexeeva, O., Baranovsky, A., Bunkova, E., Burnevich, E., Dolgikh, O., Grinevich, V., Lakhin, A., Tarabar, D., Ling, KL., Bunganic, I., Cernok, S., Gregus, M., Coetzer, T., Grundling, H., Moola, SA., Wright, JP., Ziady, C., Bermejo, F., Calvet, X., Herrerias, JM., Perez Calle JL., Perez Gisbert, J., Hertervig, E., Karlen, P., Michetti, P., Rogler, G., Seibold, F., Wu, DC., Atug, O., Kurdas, OO., Datsenko, O., Dorofyeyev, A., Dudar, L., Golovchenko, O., Klyarits'ka, I., Skrypnyk, I., Hawthorne, AB., Middleton, S., Abreu, M., Bala, N., Becker, S., Behm, B., Braun, R., Bukhari, M., Chen, S., Coates, A., Dar, S., Dassopoulos, T., De Villiers, W., Desautels, S., Desta, T., Dimitroff, J., Dryden, G., Duvall, A., Farraye, F., Fein, S., Liu, BF., Gatof, D., Geenen, D., Ginsburg, P., Glombicki, A., Glover, S., Gordon, G., Grisolano, S., Hanauer, S., Hanson, J., Hardi, R., Hoffman, B., Isaacs, K., Kim, C., Koval, G., Lashner, B., Lawitz, E., Lee, S., Leman, B., Levine, J., Loftus, E., Mahadevan, U., Mannon, P., Marcet, J., Matsuyama, R., Matusow, G., McCabe, R., Mirkin, K., Murphy, M., Mushahwar, A., Mutlu, E., Nagrani, M., Nguyen, D., Nichols, M., Nieves Ramirez, A., Oubre, B., Pace, S., Pandak, W., Perera, L., Quadri, A., Quallich, L., Rajapakse, R., Randall, C., Regueiro, M., Safdi, A., Sandborn, W., Sands, B., Saubermann, L., Scherl, E., Schwartz, D., Sedghi, S., Shafran, I., Shepard, R., Siegel, C., Stein, L., Tatum, H., Triebling, A., Vasudeva, R., Winston, B., Wolf, D., Younes, Z., Feagan, BG., Colombel, JF., Rutgeerts, P., Sandborn, WJ., Sands, BE., Jewell, D., Mahon, J., Rothstein, R., Snydman, D., Massaro, J., Clifford, D., Berger, J., Major, E., Provenzale, J., Lev, M., and Medical Microbiology & Infectious Diseases

Subjects
Adult, Male, Integrins, medicine.medical_specialty, HUMAN POLYOMAVIRUSES, JC, Antibodies/blood, Antibodies, Monoclonal, Humanized/adverse effects, Antibodies, Monoclonal, Humanized/immunology, Crohn Disease/drug therapy, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Glucocorticoids/therapeutic use, Humans, Immunosuppressive Agents/therapeutic use, Induction Chemotherapy, Infusions, Intravenous/adverse effects, Integrins/antagonists & inhibitors, Integrins/immunology, Maintenance Chemotherapy, Middle Aged, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, Antibodies, Monoclonal, Humanized, Placebo, Gastroenterology, Inflammatory bowel disease, Antibodies, Vedolizumab, CERTOLIZUMAB PEGOL, Natalizumab, Crohn Disease, Maintenance therapy, HUMANIZED ANTIBODY, Internal medicine, Ustekinumab, medicine, Certolizumab pegol, Infusions, Intravenous, Glucocorticoids, NATALIZUMAB, business.industry, Induction chemotherapy, General Medicine, medicine.disease, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, RELAPSING MULTIPLE-SCLEROSIS, INFLAMMATORY-BOWEL-DISEASE, HUMAN POLYOMAVIRUSES, HUMANIZED ANTIBODY, CERTOLIZUMAB PEGOL, ULCERATIVE-COLITIS, RANDOMIZED-TRIAL, NATALIZUMAB, JC, RANDOMIZED-TRIAL, digestive system diseases, Surgery, ULCERATIVE-COLITIS, RELAPSING MULTIPLE-SCLEROSIS, business, Immunosuppressive Agents, INFLAMMATORY-BOWEL-DISEASE, medicine.drug
Abstract

BACKGROUND: The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P

Published
2013

13. Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

Author

Pineton de Chambrun G Body-Malapel M Frey-Wagner I ..... Rogler G Colombel JF .... Desreumaux P

Subjects
complex mixtures
Abstract

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 246 trinitrobenzene sulfonic acid and dextran sodium sulfate induced colitis and chronic colitis in interleukin 10 negative (IL10( / )) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation colonic myeloperoxidase activity inflammatory cytokines expression and decreased the epithelial cell renewal compared with control animals. Under basal conditions aluminum impaired intestinal barrier function. In vitro aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor.

Published
2014

14. Methotrexate for Corticosteroid- Dependent Ulcerative Colitis: Results of a Placebo Randomized Controlled Trial

Author

Carbonnel F, Colombel JF, Filippi J, Katsanos K, Peyrin-Biroulet L, Allez M, Nachury M, Novacek G, Danese S, Abitbol V, Bossa F, Moreau J, Bommelaer G, Bourreille A, Dupas JL, Roblin X, Bouhnik Y, Reinisch W, Farkkila MA, Brixi H, Seksik P, Malamut G, Coulibaly B, Dewit O, Louis E, Deplanque D, Michetti PF, Sarter H, Laharie D, Carbonnel, F, Colombel, Jf, Filippi, J, Katsanos, K, Peyrin-Biroulet, L, Allez, M, Nachury, M, Novacek, G, Danese, S, Abitbol, V, Bossa, F, Moreau, J, Bommelaer, G, Bourreille, A, Dupas, Jl, Roblin, X, Bouhnik, Y, Reinisch, W, Farkkila, Ma, Brixi, H, Seksik, P, Malamut, G, Coulibaly, B, Dewit, O, Louis, E, Deplanque, D, Michetti, Pf, Sarter, H, and Laharie, D

Published
2015

16. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial

Author

Colombel, Jf, Panaccione, R, Bossuyt, P, Lukas, M, Baert, F, Vanasek, T, Danalioglu, A, Novacek, G, Armuzzi, Alessandro, Hebuterne, X, Travis, S, Danese, Silvio, Reinisch, W, Sandborn, Wj, Rutgeerts, P, Hommes, D, Schreiber, S, Neimark, E, Huang, Bd, Zhou, Q, Mendez, P, Petersson, J, Wallace, K, Robinson, Am, Thakkar, Rb, D'Haens, G, Armuzzi, A (ORCID:0000-0003-1572-0118), Danese, S, Colombel, Jf, Panaccione, R, Bossuyt, P, Lukas, M, Baert, F, Vanasek, T, Danalioglu, A, Novacek, G, Armuzzi, Alessandro, Hebuterne, X, Travis, S, Danese, Silvio, Reinisch, W, Sandborn, Wj, Rutgeerts, P, Hommes, D, Schreiber, S, Neimark, E, Huang, Bd, Zhou, Q, Mendez, P, Petersson, J, Wallace, K, Robinson, Am, Thakkar, Rb, D'Haens, G, Armuzzi, A (ORCID:0000-0003-1572-0118), and Danese, S

Abstract

Background Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm.Methods CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1: 1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (< 70 kg or >= 70 kg), and disease duration (<= 2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin >= 250 mu g/g, C-reactive protein >= 5mg/L, CDAI >= 150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of < 70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI

Published
2017

18. Ustekinumab as induction and maintenance therapy for Crohn's disease

Author

Feagan, Bg, Sandborn, Wj, Gasink, C, Jacobstein, D, Lang, Y, Friedman, Jr, Blank, Ma, Johanns, J, Gao, Ll, Miao, Y, Adedokun, Oj, Sands, Be, Hanauer, Sb, Vermeire, S, Targan, S, Ghosh, S, de Villiers WJ, Colombel, Jf, Tulassay, Z, Seidler, U, Salzberg, Ba, Desreumaux, P, Lee, Sd, Loftus EV Jr, Dieleman, La, Katz, S, Rutgeerts, P, Bampton, P, Chung, A, Connor, S, Debinski, H, Leong, R, Macrae, F, Pavli, P, Sorrentino, D, van den Bogaerde, J, Vogel, W, Vogelsang, H, Louis, E, Mana, F, Zaltman, C, Aumais, G, Bernstein, C, Bressler, B, Dhalla, S, Dieleman, L, Feagan, B, Marshall, J, Panaccione, R, Ropeleski, M, Stehlik, J, Volfova, M, Brynskov, J, Glerup, H, Abitbol-Selinger, V, Allez, M, Beaugerie, L, Bourreille, A, Cadiot, G, Dupas, J, Grimaud, J, Laharie, D, Lerebours, E, Moreau, J, Baumgart, D, Brand, S, Ebert, M, Ehehalt, R, Hasselblatt, P, Howaldt, S, Klaus, J, Krummenerl, P, Kucharzik, T, Lügering, A, Mudter, J, Preiss, J, Schreiber, S, Stallmach, A, Stein, J, Strauch, U, Salamon, A, Patchett, S, Lahat-Zok, A, Rachmilewitz, D, Annese, V, Bossa, F, Guidi, L, Kohn, A, Rocca, R, Ando, A, Ashida, T, Hanai, H, Ishida, T, Ito, H, Matsumoto, T, Motoya, S, Nakamura, S, Sameshima, Y, Suzuki, Y, Watanabe, K, Yamagami, H, Yamamoto, T, Yao, K, Kim, H, Kim, Y, D'Haens, G, Pierik, M, van Bodegraven, A, van der Woude CJ, Gearry, R, Ciecko-Michalska, I, Malecka-Panas, E, Jojic, N, Aboo, N, Wright, J, Arranz, M, Viso, L, Ahmad, T, Bloom, S, Campbell, S, Creed, T, Cummings, F, Hawthorne, B, Iqbal, T, Ireland, A, Parkes, M, Pollok, R, Shaw, I, Shonde, A, Smith, M, Steel, A, Subramanian, S, Travis, S, Tremelling, M, Aberra, F, Abraham, B, Barish, C, Behm, B, Birbara, C, Bochner, R, Bologna, S, Brant, S, Charles, R, Cohen, N, de Villers, W, Dryden, G, Duvall, A, Flasar, M, Fleisher, M, Florez, D, Fogel, R, Gagneja, H, Gross, C, Hamilton, J, Hanauer, S, Hanson, J, Hardi, R, Higgins, P, Isaacs, K, Katz, J, Kaur, N, Khan, N, Lee, S, Leman, B, Levenson, S, Lichtiger, S, Loftus, E, Malik, P, Mcnair, A, Melmed, G, Miner, P, Nichols, M, Noar, M, Oikonomou, I, Oubre, B, Peterson, K, Pruitt, R, Quirk, D, Safdi, A, Safdi, M, Salzberg, B, Sandborn, W, Saubermann, L, Scherl, E, Schwartz, D, Schwarz, R, Sedghi, S, Selby, L, Shafran, I, Siegel, C, Sninsky, C, Stern, M, Stockwell, D, Stone, C, Swaminath, A, Swoger, J, Taormina, M, Williams, E, Winstead, N, Wolf, D, Wolosin, J, Yacyshyn, B, Yajnik, V, Yen, E, Hetzel, D, Muls, V, Bafutto, M, Francesconi, C, Sipahi, A, Steinwurz, F, Churchev, J, Kotzev, I, Marinova, I, Penchev, P, Spassova, Z, Stoinov, S, Takov, D, Vassileva, G, Fowler, S, Greenberg, G, Jones, J, Saibil, F, Salh, B, Banić, M, Duvnjak, M, Stimac, D, Goujon, G, Pelletier, A, Peyrin-Biroulet, L, Aldinger, V, Bokemeyer, B, Büning, C, Konturek, J, Krummenerl, T, Ochsenkuehn, T, Altorjay, I, Kis, J, Pecsi, G, Székely, A, Varga, M, Vincze, A, Wacha, J, Oddsson, E, Orvar, K, Avni-Biron, I, Fishman, S, Fraser, G, Konikoff, F, Melzer, E, Oren, R, Shirin, H, Danese, S, Marino, M, Sturniolo, Gc, Horiki, N, Iijima, H, Iwabuchi, M, Kanai, T, Kunisaki, R, Maemoto, A, Matsuoka, K, Osada, T, Sugimoto, K, Tanaka, S, Cheon, Jh, Han, Ds, Jang, Bi, Kim, Hj, Kim, Js, Kim, Yh, Park, Sj, Yang, Sk, Arnold, M, Claydon, A, Haines, M, Hill, J, Rowbotham, D, Schultz, M, Wallace, I, Bochenek, A, Niezgoda, K, Szura, M, Arutyunov, G, Baranovsky, A, Khalif, I, Osipenko, M, Milinic, N, Bloch, H, Kruger, Fc, Prins, M, Watermeyer, G, Ziady, C, Calvo, Xc, Domínguez-Muñoz, Je, Gisbert, Jp, Arsenescu, R, Beaulieu, D, Bedford, R, Behrend, C, Cleavinger, P, Cohen, J, Ertan, A, Freilich, B, Friedenberg, K, Glover, S, Gordon, G, Gunaratnam, N, Gupta, N, Holbrook, R, Jones, M, Kaufman, B, Khan, Nh, Khurana, S, Legnani, P, Mutlu, E, Phillips, R, Rai, R, Reichelderfer, M, Ritter, T, Safdi, Ma, Sands, B, Schulman, M, Smith, J, Suiter, D, Taylor, D, Vasudeva, R, Winstead, T, Zwick, A, Savoye, G, Atreya, R, Ochsenkuhn, T, Ott, C, Goldin, E, Motohiro, E, Takanori, K, Park, S, James, B, Cummings, J, Tariq, A, Willert, R, Allan, M, Bulat, R, Devilliers, W, Eaker, E, Hou, J, Mendu, S, Nicols, M, Proctor, D, Thosani, N, Zhang, C, and UNITI-IM-UNITI Study Group

Subjects
030203 arthritis & rheumatology, Adult, Male, Infusions, Medicine (all), Remission Induction, Crohn Disease, Female, Humans, Induction Chemotherapy, Infusions, Intravenous, Maintenance Chemotherapy, Middle Aged, Ustekinumab, General Medicine, Orvostudományok, Klinikai orvostudományok, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Intravenous
Abstract

Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of ≥100 points or a CDAI score150). The primary end point for the maintenance trial was remission at week 44 (CDAI score150).The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P=0.005 and P=0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups.Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329 , NCT01369342 , and NCT01369355 .).

Published
2016

19. OC-043 Long term efficacy and safety of ustekinumab for crohn’s disease: results from im-uniti long-term extension through 2 years

Author

Sandborn, WJ, primary, Rutgeerts, P, additional, Gasink, C, additional, Jacobstein, D, additional, Gao, L, additional, Johanns, J, additional, Sands, B, additional, Hanauer, S, additional, Targan, S, additional, Ghosh, S, additional, Villiers, WJS de, additional, Colombel, JF, additional, and Feagan, BG, additional

Published
2017
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20. The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

Author

Torres, J, primary, Palmela, C, additional, Brito, H, additional, Bao, X, additional, Ruiqi, H, additional, Moura-Santos, P, additional, Pereira da Silva, J, additional, Oliveira, A, additional, Vieira, C, additional, Perez, K, additional, Itzkowitz, SH, additional, Colombel, JF, additional, Humbert, L, additional, Rainteau, D, additional, Cravo, M, additional, Rodrigues, CM, additional, and Hu, J, additional

Published
2017
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21. Vedolizumab as induction and maintenance therapy for ulcerative colitis

Author

Feagan, Bg, Rutgeerts, P, Sands, Be, Hanauer, S, Colombel, Jf, Sandborn, Wj, Van Assche, G, Axler, J, Kim, Hj, Danese, S, Fox, I, Milch, C, Sankoh, S, Wyant, T, Xu, J, Parikh, A, Bampton P, GEMINI 1 Study G. r. o. u. p., Chung, A, Debinski, H, Florin, T, Hetzel, D, Kronborg, I, Lawrance, I, Leong, R, Macrae, F, Moore, G, Pavli, P, Radford Smith, G, Weltman, M, Haas, T, Reinisch, W, Stockenhuber, F, Vogel, W, De Maeyer, M, De Vos, M, D'Haens, G, Louis, E, Muls, V, Petrov, P, Aumais, G, Bitton, A, Bourdages, R, Bressler, B, Cohen, A, Fedorak, R, Greenberg, G, Jones, J, Kutcher, W, Macintosh, D, Ponich, T, Singh, R, Steinhart, H, Sy, R, Douda, L, Lukas, M, Samek, M, Vyhnalek, P, Woznica, V, Zadorova, Z, Andersen, V, Rannem, T, Staun, M, Maelt, A, Margus, B, Bonaz, B, Coffin, B, Desreumaux, P, Laharie, D, Reimund, Jm, Karaus, M, Pace, A, Ross, M, Schmidt, W, Witthoeft, T, Zeitz, M, Karamanolis, D, Mantzaris, G, Maris, T, Ng, C, Gall, J, Hunyady, B, Szepes, A, Toth, T, Vincze, A, Oddsson, E, Jósefsspktali, Kö, Ahuja, V, Amarapurkar, D, Goenka, M, Habeeb, Ma, Jalihal, U, Kalambe, B, Koshy, A, Kumar, R, Prasad, V, Reddy, N, Sekar, T, Shankar, R, Tantry, V, Ryan, B, Avni, Y, Ben Horin, S, Ardizzone, S, Armuzzi, A, Corazziari, E, Fries, Walter, Kohn, A, Lisova, D, George, Am, Hilmi, In, Bhaskaran, Sk, Soon, Sy, Engels, L, Ponsioen, C, Wallace, I, Wyeth, J, Florholmen, J, Jahnsen, J, Lygren, I, Röseth, A, Ciecko Michalska, I, Gonciarz, M, Huk, J, Jamrozik Kruk, Z, Kondusz Szklarz, M, Paradowski, L, Wiechowska Kozlowska, A, Han, Ds, Hong, Sp, Kim, Js, Kim, Ko, Kim, Yh, Yang, Sk, Alexeeva, O, Bunkova, E, Burnevich, E, Dolgikh, O, Kasherininova, I, Khovaeva, Y, Lakhin, A, Ling, Kl, Bester, F, Coetzer, T, Grundling Hde, K, Jackson, Ld, Spies, P, Wright, Jp, Ziady, C, Garcia Planella, E, Perez Gisbert, J, Rogler, G, Seibold, F, Kao, Aw, Wu, Dc, Atug, O, Kurdas, Oo, Hawthorne, Ab, Lindsay, J, Abreu, M, Aggarwal, A, Bala, N, Becker, S, Behm, B, Braun, R, Cohn, W, Cross, R, Dar, S, Dassopoulos, T, De Villiers, W, Desta, T, Dryden, G, Duvall, A, Farraye, F, Fein, S, Liu, Bf, Gatof, D, Geenen, D, Ginsburg, P, Glover, S, Gopal, V, Hanson, J, Hardi, R, Isaacs, K, Jain, R, Karyotakis, N, Korzenik, J, Koshy, G, Koval, G, Lawitz, E, Lee, S, Loftus, E, Luther, R, Mahadevan, U, Mannon, P, Matsuyama, R, Mcintosh, A, Melmed, G, Mirkin, K, Nichols, M, Oubre, B, Pandak, W, Quadri, A, Quallich, L, Randall, C, Rausher, D, Regueiro, M, Safdi, A, Sands, B, Scherl, E, Schneier, J, Schwartz, D, Sedghi, S, Shafran, I, Siegel, C, Stein, L, Tatum, H, Weinberg, D, Winston, B, Wolf, D, Younes, Z, Jewell, D, Mahon, J, Rothstein, R, Snydman, D, Massaro, J, Clifford, D, Berger, J, Major, E, Provenzale, J, Abstract, Lev M., Feagan, Bg, Rutgeerts, P, Sands, Be, Hanauer, S, Colombel, Jf, Sandborn, Wj, Van Assche, G, Axler, J, Kim, Hj, Danese, S, Fox, I, Milch, C, Sankoh, S, Wyant, T, Xu, J, and Parikh, A

Subjects
Adult, Male, medicine.medical_specialty, Integrins, Placebo, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, law.invention, Vedolizumab, Maintenance Chemotherapy, Maintenance therapy, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Humans, Glucocorticoids, Aged, business.industry, General Medicine, Induction Chemotherapy, Middle Aged, medicine.disease, Ulcerative colitis, Infliximab, Surgery, Clinical trial, Cohort, Colitis, Ulcerative, Drug Therapy, Combination, Female, business, Immunosuppressive Agents, medicine.drug
Abstract

Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups.Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).

Published
2013

22. Distribution of Crohn's disease susceptibility haplotypes in European families

Author

Zouali, H., Lesage, S., Chamaillard, M., Czard, JP., Belaiche, J., Almer, S., Tysk, C., O'Morain, C., Gassul, M., Modigliani, R., Colombel, JF., Sahbatou, M., Thomas, G., and Hugot, JP.

Subjects
Human genetics -- Research, Human chromosome abnormalities -- Research, Genetic disorders -- Research, Crohn's disease -- Genetic aspects, Biogeography -- Genetic aspects, Biological sciences
Published
2001

23. Review article: infliximab for Crohn's disease treatment - shifting therapeutic strategies after 10 years of clinical experience

Author

Danese S, Colombel JF, Reinisch W, Rutgeerts PJ, Fiorino, Gionata, Danese, S, Colombel, Jf, Reinisch, W, Rutgeerts, Pj, and Fiorino, Gionata

Abstract

P>Background Crohn's disease is a progressive condition, with most patients developing a penetrating or stricturing complication over time. A decade ago, treatment goals consisted of immediate symptomatic control. The introduction of anti-tumour necrosis factor (anti-TNF) therapies, however, has changed the way patients with Crohn's disease are treated. Over 10 years of clinical data and experience have demonstrated these therapies to be highly effective in Crohn's disease. Aim To provide clinicians guidance on optimising treatment with anti-TNF therapies in Crohn's disease by introducing an evidence- and personal opinion-based treatment algorithm using infliximab initial anti-TNF therapy. Methods Scientific literature was reviewed using MEDLINE to evaluate data on clinical trials with infliximab in luminal and fistulising Crohn's disease. Results The data from several landmark infliximab trials have changed clinical practice and led to a readjustment of treatment goals in Crohn's disease, allowing patients to achieve more than just symptomatic relief including sustained steroid-free remission. Infliximab induces complete mucosal healing and reduces the rates of hospitalisation and surgery. Based on disease-related risk factors, a treatment algorithm for infliximab is delineated in favour of a rapid step-up approach in patients at high risk for a disabling course of disease. Conclusion Adopting the suggested treatment algorithm for infliximab into clinical routine is aimed to optimise outcomes for patients with Crohn's disease.

Published
2011

24. Patient Reported Outcomes (PROs) können zur Überprüfung des anhaltenden klinischen Ansprechens auf Golimumab (GLM) bei Patienten mit mäßiger bis schwerer aktiver Colitis Ulcerosa herangezogen werden: Ergebnisse der PURSUIT Maintenance Studie

Author

Reinisch, W, primary, Colombel, JF, additional, Feagan, BG, additional, Han, C, additional, Marano, C, additional, Strauss, R, additional, Gibson, P, additional, Sandborn, WJ, additional, Huyck, S, additional, Cornillie, F, additional, and Rutgeerts, P, additional

Published
2016
Full Text
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25. Pénétration dans les structures coliques de la pipéracilline utilisée en prophylaxie dans la chirurgie colorectale

Author

Husson Mo, Colombel Jf, P. Vincent, P. Quandale, F. Jehl, G. Arbon, and D. Lescut

Subjects
Gynecology, medicine.medical_specialty, Infectious Diseases, business.industry, Medicine, business, Tissue penetration
Abstract

Resume La penetration de la piperacilline (4 g IVD) dans les structures coliques a ete etudiee chez dix-huit patients (7 hommes, 11 femmes, 61 ± 16 ans) operes pour un adenocarcinome lieberkuhnien colique ou rectal. Dans les ganglions peri-coliques, les concentrations moyennes de piperacilline etaient de 25,6 ± 21,5 et 18,0 ± 21,5 μg/g respectivement 41,9 ± 13,7 et 91,1 ± 26,1 minutes apres l'administration. Dans la paroi colique, ces concentrations etaient de 26,9 ± 24,5 et 11,9 ± 12,6 μg/g respectivement 91,1 ± 26,1 et 171,6 ± 26,7 minutes apres l'administration. Ces concentrations sont nettement superieures aux CMI90 de la piperacilline vis-a-vis des bacteries visees par l'antibioprophylaxie de la chirurgie colorectale, a savoir les enterobacteries, l'enterocoque et Bacteroides fragilis .

Published
1995

26. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Author

Jostins, Luke, Ripke, Stephan, Weersma, Rinse K., Duerr, Richard H., Mcgovern, Dermot P., Hui, Ken Y., Lee, James C., Philip Schumm, L., Sharma, Yashoda, Anderson, Carl A., Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L., Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Andrews, Jane M., Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A., Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D'Amato, Mauro, De Jong, Dirk, Devaney, Kathy L., Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R., Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Xinli, Hu, Karlsen, Tom H., Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R., Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Regueiro, Miguel, Rotter, Jerome I., Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A., Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kent D., Tremelling, Mark, Verspaget, Hein W., De Vos, Martine, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhao, Hongyu, Silverberg, Mark S., Annese, Vito, Hakonarson, Hakon, Brant, Steven R., Radford Smith, Graham, Mathew, Christopher G., Rioux, John D., Schadt, Eric E., Daly, Mark J., Franke, Andre, Parkes, Miles, Vermeire, Severine, Barrett, Jeffrey C., Cho, Judy H., Barclay, M, Peyrin Biroulet, L, Chamaillard, M, Colombel, Jf, Cottone, M, Croft, A, D'Incà, R, Halfvarson J, Hanigan K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lémann, M, Levine, A, Massey, D, Milla, M, Montgomery, Gw, Ng, Sm, Oikonomou, I, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, Laura, Taylor, Km, Törkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Andrews, Jm, Bampton, Pa, Florin, Th, Gearry, R, Krishnaprasad, K, Lawrance, Ic, Mahy, G, Radford Smith, G, Roberts, Rl, Simms, La, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie AM 3rd, Beck, K, Bernard, Ej, Binion, Dg, Bitton, A, Brant, Sr, Cho, Jh, Cohen, A, Croitoru, K, Daly, Mj, Datta, Lw, Deslandres, C, Duerr, Rh, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, Gr, Haritunians, T, Jobin, G, Katz, S, Lahaie, Rg, Mcgovern, Dp, Nelson, L, Ning, K, Paré, P, Regueiro, Md, Rioux, Jd, Ruggiero, E, Schumm, L, Schwartz, M, Scott, R, Sharma, Y, Silverberg, Ms, Spears, D, Steinhart, A, Stempak, Jm, Swoger, Jm, Tsagarelis, C, Zhang, C, Zhao, H, Aerts, J, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, Sg, Balmforth, Aj, Barnes, C, Barrett, Jc, Barroso, I, Barton, A, Bennett, Aj, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, Oj, Braund, Ps, Bredin, F, Breen, G, Brown, Mj, Bruce, In, Bull, J, Burren, Os, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, Cm, Coffey, Aj, Connell, Jm, Conrad, Df, Cooper, Jd, Dominiczak, Af, Downes, K, Drummond, He, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, Dm, Evans, G, Eyre, S, Farmer, A, Ferrier, In, Flynn, E, Forbes, A, Forty, L, Franklyn, Ja, Frayling, Tm, Freathy, Rm, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon Smith, K, Gray, E, Green, E, Groves, Cj, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, Ga, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, Jm, Hughes, D, Hunt, S, Isaacs, Jd, Jain, M, Jewell, Dp, Johnson, T, Jolley, Jd, Jones, Ir, Jones, La, Kirov, G, Langford, Cf, Lango Allen, H, Lathrop, Gm, Lee, J, Lee, Kl, Lees, C, Lewis, K, Lindgren, Cm, Maisuria Armer, M, Maller, J, Mansfield, J, Marchini, Jl, Martin, P, Massey, Dc, Mcardle, Wl, Mcguffin, P, Mclay, Ke, Mcvean, G, Mentzer, A, Mimmack, Ml, Morgan, Ae, Morris, Ap, Mowat, C, Munroe, Pb, Myers, S, Newman, W, Nimmo, Er, O'Donovan, Mc, Onipinla, A, Ovington, Nr, Owen, Mj, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, Jr, Phillips, A, Plagnol, V, Prescott, Nj, Prokopenko, I, Quail, Ma, Rafelt, S, Rayner, Nw, Reid, Dm, Renwick, A, Ring, Sm, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, Jg, Sanderson, Jd, Sawcer, Sj, Schuilenburg, H, Scott, Ce, Seal, S, Shaw Hawkins, S, Shields, Bm, Simmonds, Mj, Smyth, Dj, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, He, Stirrups, K, Stone, Ma, Strachan, Dp, Su, Z, Symmons, Dp, Thompson, Jr, Thomson, W, Tobin, Md, Travers, Me, Turnbull, C, Vukcevic, D, Wain, Lv, Walker, M, Walker, Nm, Wallace, C, Warren Perry, M, Watkins, Na, Webster, J, Weedon, Mn, Wilson, Ag, Woodburn, M, Wordsworth, Bp, Yau, C, Young, Ah, Zeggini, E, Brown, Ma, Burton, Pr, Caulfield, Mj, Compston, A, Farrall, M, Gough, Sc, Hall, As, Hattersley, At, Hill, Av, Mathew, Cg, Pembrey, M, Satsangi, J, Stratton, Mr, Worthington, J, Hurles, Me, Duncanson, A, Ouwehand, Wh, Parkes, M, Rahman, N, Todd, Ja, Samani, Nj, Kwiatkowski, Dp, Mccarthy, Mi, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, Jm, Bramon, E, Casas, Jp, Corvin, A, Jankowski, J, Markus, Hs, Palmer, Cn, Plomin, R, Rautanen, A, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Genome-wide association study, Disease, SUSCEPTIBILITY, Inflammatory bowel disease, NUMBER, 0302 clinical medicine, Crohn Disease, NETWORK, Genetics, 0303 health sciences, Multidisciplinary, Genomics, Ulcerative colitis, 3. Good health, Colitis, Ulcerative, Genetic Predisposition to Disease, Genome, Human, Haplotypes, Humans, Inflammatory Bowel Diseases, Mycobacterium, Mycobacterium Infections, Mycobacterium tuberculosis, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, Genome-Wide Association Study, Host-Pathogen Interactions, IRGM, Medical genetics, 030211 gastroenterology & hepatology, EXPRESSION, medicine.medical_specialty, Immunology, Biology, Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2], TUBERCULOSIS, 03 medical and health sciences, Medical research, medicine, Allele, METAANALYSIS, 030304 developmental biology, HYPER-IGE SYNDROME, MUTATIONS, medicine.disease, RISK LOCI, Genetic architecture, digestive system diseases
Abstract

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Published
2012

27. Ustekinumab induction and maintenance therapy in refractory Crohn's disease

Author

Sandborn, Wj, Gasink, C, Gao, Ll, Blank, Ma, Johanns, J, Guzzo, C, Sands, Be, Hanauer, Sb, Targan, S, Rutgeerts, P, Ghosh, S, de Villiers WJ, Panaccione, R, Greenberg, G, Schreiber, S, Lichtiger, S, Feagan, Bg, Haas, T, Kaser, A, Vogelsang, H, Brown, S, Florin, T, Gibson, Pg, Hetzel, D, Leong, R, Pavli, P, Radford-Smith, G, Sparrow, M, Baert, F, D'Haens, G, D'Heygere, F, Franchimont, D, Louis, E, Mana, F, Moreels, T, Vermeire, S, Anderson, F, Axler, J, Greenbloom, S, Bitton, A, Fedorak, Rn, Larkai, E, Marshall, J, Singh, R, Abitbol, V, Allez, M, Lemann, M, Bonaz, B, Colombel, Jf, Dupas, Jl, Hebuterne, X, Laharie, D, Lerebours, E, Moreau, J, Bokemeyer, B, Holler, B, Howaldt, Sp, Krummenerl, T, Kucharzik, T, Ochsenkühn, T, Raedler, A, Schiefke, I, Seidler, U, Sturm, A, Zeitz, M, Eliakim, A, Fishman, S, Konikoff, Fm, Lavy, A, Niv, Y, Nussinson, E, Rachmilewitz, D, Andriulli, A, Annese, V, Biancone, L, Corazza, Gr, Danese, S, Sturniolo, Gc, Terrosu, G, Sorrentino, D, Hommes, Dw, Jansen, Jm, Otten, Mh, Pierik, M, Ponsioen, Cy, Stokkers, P, van Bodegraven AA, Van der Woude, J, Calvet Calvo, X, Casellas, F, Garcia López, S, Garcia-Planella, E, Ginard-Vincens, D, López San Román, A, Muñoz Nuñez, F, Pérez Gisbert, J, Vera, Mi, Rodrigo, J, Riestra-Menendez, S, Arnott, I, Bloom, S, Campbell, Ss, Harbord, Mw, Mansfield, Jc, Nwokolo, C, Parkes, M, Probert, Cs, Aberra, Fn, Abraham, Bp, Abreu, Mt, Amontree, Js, Barish, Cf, Barto, Ae, Behm, B, Birbara, Ca, Bologna, S, Dryden GW Jr, Eisner, Ms, Ertan, A, Fogel, R, Gagneja, Hk, Ginsburg, P, Goff, Js, Gordon, G, Hamilton, Jw, Hanson, Js, Hardi, R, Hemaidan, A, Higgins, P, Holderman, W, Hornbuckle, K, Ibegbu, E, Isaacs, Kl, Katz, Ja, Katz, S, Kaufman, Bp, Kavanaugh, Af, Khurana, Sk, Lashner, B, Lawrence, S, Hansen, Rn, Lee, S, Leighton, Ja, Leman, Bi, Levenson, Sd, Lowe, Je, Marcuard, Sp, Matsuyama, Rm, Mcnair, Ae, Melmed, G, Miller, Km, Miner PB Jr, Mutlu, Ea, Keshavarzian, A, Narayen, V, Noar, Md, Patel, Ph, Patrick, Tj, Peck, A, Peterson, Ka, Phillips, Rw, Picco, Mf, Randall, C, Richards, Rj, Safdi, Ma, Scherl, Eh, Schwartz, Da, Schwartz, Hi, Schwartz, Jl, Sedghi, S, Shafran, I, Siegel, Ca, Sninsky, Ca, Stern, M, Suiter, D, Swaminath, A, Terdiman, Jp, Mahadevan, U, Thomson, C, Valentine, J, Vasudeva, R, Vecchio, Ja, Wolf, Dc, Yajnik, V, Yabkowski, J, Yen, E., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Other departments

Subjects
Male, Oncology, MONOCLONAL-ANTIBODY, Drug Resistance, Disease, Severity of Illness Index, Crohn Disease, Maintenance therapy, IL-23, Adult, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Double-Blind Method, Female, Humans, Induction Chemotherapy, Maintenance Chemotherapy, Middle Aged, Remission Induction, Tumor Necrosis Factors, Ustekinumab, Monoclonal, Humanized, Settore MED/12 - Gastroenterologia, Crohn's disease, EXPERIMENTAL COLITIS, General Medicine, medicine.drug, medicine.medical_specialty, MONOCLONAL-ANTIBODY, RANDOMIZED-TRIAL, EXPERIMENTAL COLITIS, CERTOLIZUMAB PEGOL, INFLAMMATION, IL-23, INTERLEUKIN-12, ADALIMUMAB, INFLIXIMAB, DISCOVERY, Antibodies, CERTOLIZUMAB PEGOL, INFLAMMATION, Refractory, Internal medicine, INFLIXIMAB, medicine, business.industry, Induction chemotherapy, medicine.disease, RANDOMIZED-TRIAL, INTERLEUKIN-12, Clinical trial, DISCOVERY, Immunology, Tumor Necrosis Factor Inhibitors, business, ADALIMUMAB
Abstract

BACKGROUND In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown. METHODS We evaluated ustekinumab in adults with moderate-to-severe Crohn's disease that was resistant to anti-tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks. RESULTS The proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P = 0.005 for the comparison with the 6-mg group). The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4%, P = 0.03) and response (69.4% vs. 42.5%, P < 0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal-cell carcinoma developed in 1 patient receiving ustekinumab. CONCLUSIONS Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.)

Published
2012

28. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease

Author

Rahier, Jf, Magro, F, Abreu, C, Armuzzi, Alessandro, Ben Horin, S, Chowers, Y, Cottone, M, De Ridder, L, Doherty, G, Ehehalt, R, Esteve, M, Katsanos, K, Lees, Cw, Macmahon, E, Moreels, T, Reinisch, W, Tilg, H, Tremblay, L, Veereman Wauters, G, Viget, N, Yazdanpanah, Y, Eliakim, R, Colombel, Jf, Armuzzi, Alessandro (ORCID:0000-0003-1572-0118), Rahier, Jf, Magro, F, Abreu, C, Armuzzi, Alessandro, Ben Horin, S, Chowers, Y, Cottone, M, De Ridder, L, Doherty, G, Ehehalt, R, Esteve, M, Katsanos, K, Lees, Cw, Macmahon, E, Moreels, T, Reinisch, W, Tilg, H, Tremblay, L, Veereman Wauters, G, Viget, N, Yazdanpanah, Y, Eliakim, R, Colombel, Jf, and Armuzzi, Alessandro (ORCID:0000-0003-1572-0118)

Abstract

no abstract available

Published
2014

29. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease

Author

Rahier, JF, Ben-Horin, S, Chowers, Y, Conlon, C, De Munter, P, D'Haens, G, Domènech, E, Eliakim, R, Eser, A, Frater, J, Gassull, M, Giladi, M, Kaser, A, Lémann, M, Moreels, T, Moschen, A, Pollok, R, Reinisch, W, Schunter, M, Stange, EF, Tilg, H, Van Assche, G, Viget, N, Vucelic, B, Walsh, A, Weiss, G, Yazdanpanah, Y, Zabana, Y, Travis, SP, and Colombel, JF

Subjects
Prevention, Vaccination, parasitic diseases, Gastroenterology, Opportunistic infections, General Medicine, Human medicine, inflammatory bowel disease, opportunistic infections, prevention, vaccination, consensus, diagnosis, management, IBD, Inflammatory bowel disease, digestive system diseases
Abstract

Consensus on the European level is brought in order to promote early prevention, diagnosis and optimal management of opportunistic infections in inflammatory bowel disease on behalf of the European Crohn's and Colitis Organisation (ECCO).

Published
2009

30. Risk factors associated with small bowel adenocarcinoma in Crohn's disease: a case-control study

Author

Piton, G., Cosnes, J., Monnet, E., Beaugerie, L., Seksik, P., Savoye, Guillaume, Cadiot, G., Flourie, B., Capelle, P., Marteau, P., Lemann, M., Colombel, Jf., Khouri, E., Bonaz, B., Carbonnel, F., Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2008

31. Vedolizumab as induction and maintenance therapy for Crohn's disease.

Author

GEMINI 2 Study Group, Bampton, P., Borody, T., Chung, A., Debinski, H., Florin, T., Hetzel, D., Jakobovits, S., Lawrance, I., Leong, R., Macrae, F., Mitchell, B., Moore, G., Pavli, P., Samuel, D., Weltman, M., Haas, T., Reinisch, W., Vogel, W., Baert, F., De Maeyer, M., De Vos, M., Dewit, O., D'Haens, G., Louis, E., Muls, V., Van Assche, G., Krastev, Z., Nikolovska, D., Petrov, P., Petrov, A., Stoinov, S., Tchernev, K., Vasileva, G., Aumais, G., Axler, J., Bailey, R., Bernstein, C., Bitton, A., Bourdages, R., Bressler, B., Cohen, A., Devroede, G., Dhalla, S., Feagan, B., Fedorak, R., Green, D., Greenberg, G., Jones, J., Larkai, E., MacIntosh, D., Panaccione, R., Ponich, T., Singh, R., Sy, R., Wiesinger, H., Albin, A., Douda, L., Horny, I., Lukas, M., Stehlik, J., Stuksa, J., Volfova, M., Vyhnalek, P., Zadorova, Z., Andersen, V., Bendtsen, F., Fallingborg, J., Rannem, T., Maelt, A., Margus, B., Salupere, R., Allez, M., Des Varennes SB., Desreumaux, P., Dupas, JL., Grimaud, JC., Hebuterne, X., Lerebours, E., Picon, L., Zerbib, F., Aldinger, V., Baumgart, D., Buening, C., Dollinger, M., Hoffmann, P., Howaldt, S., Klaus, J., Konturek, JW., Krummenerl, T., Malfertheiner, P., Schmidt, W., Schreiber, S., Seidler, U., Stallmach, A., Stremmel, W., Zeitz, M., Mantzaris, G., Triantafyllou, K., Ng, C., Bene, L., Fazekas, I., Fejes, R., Gall, J., Horvat, G., Hunyady, B., Salamon, A., Toth, T., Tulassay, Z., Varga, E., Varga, M., Varga-Szabo, L., Vincze, A., Oddsson, E., Örvar, K., Ahuja, V., Amarapurkar, D., Chandra, A., Koshy, A., Krishna, P., Ramakrishna, K., Reddy, N., Thorat, V., Patchett, S., Ryan, B., Ben Horin, S., Fishman, S., Lavy, A., Rachmilewitz, D., Ardizzone, S., Corazziari, E., Danese, S., Fries, W., Gasbarrini, A., Kohn, A., Sturniolo, GC., Danilans, A., George, AM., Hilmi, IN., Engels, LG., Ponsioen, CY., van der Woude CJ., Gearry, R., Haines, M., Schultz, M., Wallace, I., Wyeth, J., Florholmen, J., Jahnsen, J., Lygren, I., Röseth, A., Ciecko-Michalska, I., Gonciarz, M., Horynski, M., Huk, J., Jamrozik-Kruk, Z., Janke, A., Klupinska, G., Marecik, J., Paradowski, L., Rudzinski, J., Rydzewska, G., Han, DS., Hong, SP., Kim, HJ., Kim, JS., Kim, KO., Kim, YH., Yang, SK., Gheorghe, LS., Voiosu, RM., Alexeeva, O., Baranovsky, A., Bunkova, E., Burnevich, E., Dolgikh, O., Grinevich, V., Lakhin, A., Tarabar, D., Ling, KL., Bunganic, I., Cernok, S., Gregus, M., Coetzer, T., Grundling, H., Moola, SA., Wright, JP., Ziady, C., Bermejo, F., Calvet, X., Herrerias, JM., Perez Calle JL., Perez Gisbert, J., Hertervig, E., Karlen, P., Michetti, P., Rogler, G., Seibold, F., Wu, DC., Atug, O., Kurdas, OO., Datsenko, O., Dorofyeyev, A., Dudar, L., Golovchenko, O., Klyarits'ka, I., Skrypnyk, I., Hawthorne, AB., Middleton, S., Abreu, M., Bala, N., Becker, S., Behm, B., Braun, R., Bukhari, M., Chen, S., Coates, A., Dar, S., Dassopoulos, T., De Villiers, W., Desautels, S., Desta, T., Dimitroff, J., Dryden, G., Duvall, A., Farraye, F., Fein, S., Liu, BF., Gatof, D., Geenen, D., Ginsburg, P., Glombicki, A., Glover, S., Gordon, G., Grisolano, S., Hanauer, S., Hanson, J., Hardi, R., Hoffman, B., Isaacs, K., Kim, C., Koval, G., Lashner, B., Lawitz, E., Lee, S., Leman, B., Levine, J., Loftus, E., Mahadevan, U., Mannon, P., Marcet, J., Matsuyama, R., Matusow, G., McCabe, R., Mirkin, K., Murphy, M., Mushahwar, A., Mutlu, E., Nagrani, M., Nguyen, D., Nichols, M., Nieves Ramirez, A., Oubre, B., Pace, S., Pandak, W., Perera, L., Quadri, A., Quallich, L., Rajapakse, R., Randall, C., Regueiro, M., Safdi, A., Sandborn, W., Sands, B., Saubermann, L., Scherl, E., Schwartz, D., Sedghi, S., Shafran, I., Shepard, R., Siegel, C., Stein, L., Tatum, H., Triebling, A., Vasudeva, R., Winston, B., Wolf, D., Younes, Z., Feagan, BG., Colombel, JF., Rutgeerts, P., Sandborn, WJ., Sands, BE., Jewell, D., Mahon, J., Rothstein, R., Snydman, D., Massaro, J., Clifford, D., Berger, J., Major, E., Provenzale, J., Lev, M., Sandborn, W.J., Feagan, B.G., Colombel, J.F., Sands, B.E., Fedorak, R.N., Fox, I., Rosario, M., Sankoh, S., Xu, J., Stephens, K., Milch, C., Parikh, A., GEMINI 2 Study Group, Bampton, P., Borody, T., Chung, A., Debinski, H., Florin, T., Hetzel, D., Jakobovits, S., Lawrance, I., Leong, R., Macrae, F., Mitchell, B., Moore, G., Pavli, P., Samuel, D., Weltman, M., Haas, T., Reinisch, W., Vogel, W., Baert, F., De Maeyer, M., De Vos, M., Dewit, O., D'Haens, G., Louis, E., Muls, V., Van Assche, G., Krastev, Z., Nikolovska, D., Petrov, P., Petrov, A., Stoinov, S., Tchernev, K., Vasileva, G., Aumais, G., Axler, J., Bailey, R., Bernstein, C., Bitton, A., Bourdages, R., Bressler, B., Cohen, A., Devroede, G., Dhalla, S., Feagan, B., Fedorak, R., Green, D., Greenberg, G., Jones, J., Larkai, E., MacIntosh, D., Panaccione, R., Ponich, T., Singh, R., Sy, R., Wiesinger, H., Albin, A., Douda, L., Horny, I., Lukas, M., Stehlik, J., Stuksa, J., Volfova, M., Vyhnalek, P., Zadorova, Z., Andersen, V., Bendtsen, F., Fallingborg, J., Rannem, T., Maelt, A., Margus, B., Salupere, R., Allez, M., Des Varennes SB., Desreumaux, P., Dupas, JL., Grimaud, JC., Hebuterne, X., Lerebours, E., Picon, L., Zerbib, F., Aldinger, V., Baumgart, D., Buening, C., Dollinger, M., Hoffmann, P., Howaldt, S., Klaus, J., Konturek, JW., Krummenerl, T., Malfertheiner, P., Schmidt, W., Schreiber, S., Seidler, U., Stallmach, A., Stremmel, W., Zeitz, M., Mantzaris, G., Triantafyllou, K., Ng, C., Bene, L., Fazekas, I., Fejes, R., Gall, J., Horvat, G., Hunyady, B., Salamon, A., Toth, T., Tulassay, Z., Varga, E., Varga, M., Varga-Szabo, L., Vincze, A., Oddsson, E., Örvar, K., Ahuja, V., Amarapurkar, D., Chandra, A., Koshy, A., Krishna, P., Ramakrishna, K., Reddy, N., Thorat, V., Patchett, S., Ryan, B., Ben Horin, S., Fishman, S., Lavy, A., Rachmilewitz, D., Ardizzone, S., Corazziari, E., Danese, S., Fries, W., Gasbarrini, A., Kohn, A., Sturniolo, GC., Danilans, A., George, AM., Hilmi, IN., Engels, LG., Ponsioen, CY., van der Woude CJ., Gearry, R., Haines, M., Schultz, M., Wallace, I., Wyeth, J., Florholmen, J., Jahnsen, J., Lygren, I., Röseth, A., Ciecko-Michalska, I., Gonciarz, M., Horynski, M., Huk, J., Jamrozik-Kruk, Z., Janke, A., Klupinska, G., Marecik, J., Paradowski, L., Rudzinski, J., Rydzewska, G., Han, DS., Hong, SP., Kim, HJ., Kim, JS., Kim, KO., Kim, YH., Yang, SK., Gheorghe, LS., Voiosu, RM., Alexeeva, O., Baranovsky, A., Bunkova, E., Burnevich, E., Dolgikh, O., Grinevich, V., Lakhin, A., Tarabar, D., Ling, KL., Bunganic, I., Cernok, S., Gregus, M., Coetzer, T., Grundling, H., Moola, SA., Wright, JP., Ziady, C., Bermejo, F., Calvet, X., Herrerias, JM., Perez Calle JL., Perez Gisbert, J., Hertervig, E., Karlen, P., Michetti, P., Rogler, G., Seibold, F., Wu, DC., Atug, O., Kurdas, OO., Datsenko, O., Dorofyeyev, A., Dudar, L., Golovchenko, O., Klyarits'ka, I., Skrypnyk, I., Hawthorne, AB., Middleton, S., Abreu, M., Bala, N., Becker, S., Behm, B., Braun, R., Bukhari, M., Chen, S., Coates, A., Dar, S., Dassopoulos, T., De Villiers, W., Desautels, S., Desta, T., Dimitroff, J., Dryden, G., Duvall, A., Farraye, F., Fein, S., Liu, BF., Gatof, D., Geenen, D., Ginsburg, P., Glombicki, A., Glover, S., Gordon, G., Grisolano, S., Hanauer, S., Hanson, J., Hardi, R., Hoffman, B., Isaacs, K., Kim, C., Koval, G., Lashner, B., Lawitz, E., Lee, S., Leman, B., Levine, J., Loftus, E., Mahadevan, U., Mannon, P., Marcet, J., Matsuyama, R., Matusow, G., McCabe, R., Mirkin, K., Murphy, M., Mushahwar, A., Mutlu, E., Nagrani, M., Nguyen, D., Nichols, M., Nieves Ramirez, A., Oubre, B., Pace, S., Pandak, W., Perera, L., Quadri, A., Quallich, L., Rajapakse, R., Randall, C., Regueiro, M., Safdi, A., Sandborn, W., Sands, B., Saubermann, L., Scherl, E., Schwartz, D., Sedghi, S., Shafran, I., Shepard, R., Siegel, C., Stein, L., Tatum, H., Triebling, A., Vasudeva, R., Winston, B., Wolf, D., Younes, Z., Feagan, BG., Colombel, JF., Rutgeerts, P., Sandborn, WJ., Sands, BE., Jewell, D., Mahon, J., Rothstein, R., Snydman, D., Massaro, J., Clifford, D., Berger, J., Major, E., Provenzale, J., Lev, M., Sandborn, W.J., Feagan, B.G., Colombel, J.F., Sands, B.E., Fedorak, R.N., Fox, I., Rosario, M., Sankoh, S., Xu, J., Stephens, K., Milch, C., and Parikh, A.

Abstract

BACKGROUND: The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). CONCLUSIONS: Vedolizumab-treated patients with active Crohn's disease were more likely than patients rec

Published
2013

32. Deep Resequencing of GWAS Loci Identifies Rare Variants in CARD9, IL23R and RNF186 That Are Associated with Ulcerative Colitis

Author

Beaudoin, M, Goyette, P, Boucher, G, Lo, KS, Rivas, MA, Stevens, C, Alikashani, A, Ladouceur, M, Ellinghaus, D, Törkvist, L, Goel, G, Lagacé, C, Annese, V, Bitton, A, Begun, J, Brant, SR, Bresso, F, Cho, JH, Duerr, RH, Halfvarson, J, McGovern, DPB, Radford-Smith, GL, Schreiber, S, Schumm, PL, Sharma, Y, Silverberg, MS, Weersma, RK, D'Amato, M, Vermeire, S, Franke, A, Lettre, G, Xavier, RJ, Daly, MJ, Rioux, JD, Aumais, G, Bernard, EJ, Cohen, A, Deslandres, C, Lahaie, R, Paré, P, Targan, SR, Rutgeerts, P, Steinhart, AH, Ahmad, T, Anderson, CA, Baldassano, RN, Balschun, T, Barclay, M, Barrett, JC, Bayless, TM, Bis, JC, Brand, S, Bumpstead, S, Buning, C, Colombel, JF, Cottone, M, D'Inca, R, Denson, T, Dubinsky, M, Edwards, C, Florin, T, Franchimont, D, Gearry, R, Georges, M, Glas, J, van Gossum, A, Griffiths, AM, Guthery, SL, Hakonarson, H, Haritunians, T, Hugot, JP, de Jong, DJ, Jostins, L, Kugathasan, S, Kullak-Ublick, G, Latiano, A, Laukens, D, Lawrance, I, Lee, J, Lees, CW, Lemann, M, Levine, A, Libioulle, C, Louis, E, Mansfield, JC, Mathew, CG, Mitrovic, M, Montgomery, GW, Mowat, C, Newman, W, Palmieri, O, Panés, J, Parkes, M, Phillips, A, Ponsioen, CY, Potocnik, U, Prescott, NJ, Proctor, DD, Regueiro, M, Beaudoin, M, Goyette, P, Boucher, G, Lo, KS, Rivas, MA, Stevens, C, Alikashani, A, Ladouceur, M, Ellinghaus, D, Törkvist, L, Goel, G, Lagacé, C, Annese, V, Bitton, A, Begun, J, Brant, SR, Bresso, F, Cho, JH, Duerr, RH, Halfvarson, J, McGovern, DPB, Radford-Smith, GL, Schreiber, S, Schumm, PL, Sharma, Y, Silverberg, MS, Weersma, RK, D'Amato, M, Vermeire, S, Franke, A, Lettre, G, Xavier, RJ, Daly, MJ, Rioux, JD, Aumais, G, Bernard, EJ, Cohen, A, Deslandres, C, Lahaie, R, Paré, P, Targan, SR, Rutgeerts, P, Steinhart, AH, Ahmad, T, Anderson, CA, Baldassano, RN, Balschun, T, Barclay, M, Barrett, JC, Bayless, TM, Bis, JC, Brand, S, Bumpstead, S, Buning, C, Colombel, JF, Cottone, M, D'Inca, R, Denson, T, Dubinsky, M, Edwards, C, Florin, T, Franchimont, D, Gearry, R, Georges, M, Glas, J, van Gossum, A, Griffiths, AM, Guthery, SL, Hakonarson, H, Haritunians, T, Hugot, JP, de Jong, DJ, Jostins, L, Kugathasan, S, Kullak-Ublick, G, Latiano, A, Laukens, D, Lawrance, I, Lee, J, Lees, CW, Lemann, M, Levine, A, Libioulle, C, Louis, E, Mansfield, JC, Mathew, CG, Mitrovic, M, Montgomery, GW, Mowat, C, Newman, W, Palmieri, O, Panés, J, Parkes, M, Phillips, A, Ponsioen, CY, Potocnik, U, Prescott, NJ, Proctor, DD, and Regueiro, M

Abstract

Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (~14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. © 2013 Beaudoin et al.

Published
2013

33. The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

Author

Torres, J, Palmela, C, Brito, H, Bao, X, Ruiqi, H, Moura-Santos, P, Pereira da Silva, J, Oliveira, A, Vieira, C, Perez, K, Itzkowitz, SH, Colombel, JF, Humbert, L, Rainteau, D, Cravo, M, Rodrigues, CM, and Hu, J

Abstract

Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcusand Fusobacteriumgenus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes(73%) and Bacteroidetesphyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

Published
2018
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34. European evidence based consensus on the diagnosis and management of Crohn's disease: current management

Author

UCL, Travis, SPL, Stange, EF, Lémann, Marc, Oresland, T, Chowers, Y., Forbes, Alastair, D'Haens, G., Kitis, G, Cortot, A., Prantera, C, Marteau, P., Colombel, JF., Gionchetti, P, Bouhnik, Y., Tiret, E, Kroesen, J, Starlinger, M, Mortensen, NJ, UCL, Travis, SPL, Stange, EF, Lémann, Marc, Oresland, T, Chowers, Y., Forbes, Alastair, D'Haens, G., Kitis, G, Cortot, A., Prantera, C, Marteau, P., Colombel, JF., Gionchetti, P, Bouhnik, Y., Tiret, E, Kroesen, J, Starlinger, M, and Mortensen, NJ

Abstract

This second section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns treatment of active disease, maintenance of medically induced remission, and surgery. The first section on definitions and diagnosis includes the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The third section on special situations in Crohn's disease includes postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy for Crohn's disease.

Published
2006

35. Clustering of Crohn's disease within affected sibships

Author

Hugot, JP, Cezard, JP, Colombel, JF, Almer, Sven, Tysk, C, Montague, S, Gassull, M, Christensen, S, Finkel, Y, Gower-Rousseau, C, Modigliani, R, Zouali, H, Lesage, S, Chamaillard, M, Marcy, J, Thomas, G, Victor, JM, Belaiche, J, Hugot, JP, Cezard, JP, Colombel, JF, Almer, Sven, Tysk, C, Montague, S, Gassull, M, Christensen, S, Finkel, Y, Gower-Rousseau, C, Modigliani, R, Zouali, H, Lesage, S, Chamaillard, M, Marcy, J, Thomas, G, Victor, JM, and Belaiche, J

Abstract

Crohn's disease (CD) is a complex genetic disorder for which aetiology is unknown. Recently, genetic factors for susceptibility have been described. Several genetic loci have been mapped and partially explain the familial aggregations of the disease. However, environmental factors may also contribute to these aggregations. We considered that if the role of non-genetic factors was negligible, CD patients would be randomly distributed in sibships with multiple affected siblings. On the other hand if there was a significant environmental contribution, the siblings would be affected non-randomly over exposure status. In order to test this hypothesis, we studied 102 sibships with two or more affected siblings. A statistical test, named Cluster of Affected Sibling Test or CAST, was developed, based on the exact calculation of the probability of observing a given number of clusters of affected siblings in multiplex families. The null hypothesis of a random distribution of affected siblings was rejected (P=0,005). The observed excess of affected sibling clusters indicates that birth order influences the disease status. Considering that an adjacent order of birth is a global estimate of environmental sharing, this observation strongly suggests that environmental factors contribute to the observed familial aggregations of the disease. This observation provides evidence that familial CD is a relevant tool for further studies of environmental factors and gene-environment interaction. More generally, the CAST statistics may be widely applicable to estimate the involvement of environmental factors in the aetiology of other binary traits which may be observed in multiple members of the same sibship.

Published
2003
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36. CARD4/NOD1 is not involved in inflammatory bowel disease

Author

Zouali, H, Lesage, S, Merlin, F, Cezard, JP, Colombel, JF, Belaiche, J, Almer, Sven, Tysk, C, O'Morain, C, Gassull, M, Christensen, S, Finkel, Y, Modigliani, R, Gower-Rousseau, C, Macry, J, Chamaillard, M, Thomas, G, Hugot, JP, Zouali, H, Lesage, S, Merlin, F, Cezard, JP, Colombel, JF, Belaiche, J, Almer, Sven, Tysk, C, O'Morain, C, Gassull, M, Christensen, S, Finkel, Y, Modigliani, R, Gower-Rousseau, C, Macry, J, Chamaillard, M, Thomas, G, and Hugot, JP

Abstract

Background and aims: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic Factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. Patients and methods: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. Results: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. Conclusion: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.

Published
2003
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38. Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease

Author

Zouali, H, Chamaillard, M, Lesage, S, Cezard, JP, Colombel, JF, Belaiche, J, Almer, Sven, Tysk, C, Montague, S, Gassull, M, Christensen, S, Finkel, Y, Gower-Rousseau, C, Modigliani, R, Macry, J, Selinger-Leneman, H, Thomas, G, Hugot, JP, Zouali, H, Chamaillard, M, Lesage, S, Cezard, JP, Colombel, JF, Belaiche, J, Almer, Sven, Tysk, C, Montague, S, Gassull, M, Christensen, S, Finkel, Y, Gower-Rousseau, C, Modigliani, R, Macry, J, Selinger-Leneman, H, Thomas, G, and Hugot, JP

Abstract

Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37 ╫ 10-4) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.

Published
2001
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40. Protective effect of CYP2D6*4 allele in ulcerative colitis disease.

Author

Lesage, S, Chamaillard, M, Colombel, JF, Belaiche, J, Cizard, JP, Tysk, C, Almer, Sven, Gassull, MA, Binder, V, Zouali, H, Thomas, G, Hugot, JP, Lesage, S, Chamaillard, M, Colombel, JF, Belaiche, J, Cizard, JP, Tysk, C, Almer, Sven, Gassull, MA, Binder, V, Zouali, H, Thomas, G, and Hugot, JP

Published
2000

41. Traitement des fistules anopérinéales dans la maladie de Crohn par injection d'une colle biologique: résultats d'un essai contrôlé randomisé

Author

Grimaud, JC, primary, Munoz-Bongrand, N, additional, Siproudhis, L, additional, Abramowitz, L, additional, Senejoux, A, additional, Vitton, V, additional, Gambiez, L, additional, Flourie, B, additional, Hebuterne, X, additional, Louis, E, additional, Coffin, B, additional, de Parades, V, additional, Lerebours, E, additional, Contou, JF, additional, Ganansia, R, additional, Bouhnik, Y, additional, Colombel, JF, additional, Mary, JY, additional, and Lemann, M, additional

Published
2007
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47. Identifying Patients With a High-risk of Relapse in Quiescent Crohns-disease

Author

UCL, Sahmoud, T., Hoctinboes, G., Modigliani, R., Bitoun, A., Colombel, JF., Soule, JC., Florent, C., Gendre, JP., Lerebours, E., Sylvester, Richard J., Mary, JY., UCL, Sahmoud, T., Hoctinboes, G., Modigliani, R., Bitoun, A., Colombel, JF., Soule, JC., Florent, C., Gendre, JP., Lerebours, E., Sylvester, Richard J., and Mary, JY.

Abstract

No reliable identification of quiescent Crohn's disease (CD) patients with a high risk of relapse is available. The aim of this study was to develop a prognostic index to identify those patients. Untreated adult patients with quiescent disease (not induced by surgery) included in three phase III clinical trials were analysed retrospectively with respect to time to relapse. Nineteen factors related to biology, disease history, and topography were investigated. A relapse was defined as either a CD Activity Index (CDAI) greater than or equal to 200, a CDAI greater than or equal to 150 but over the baseline value by more than 100, or acute complications requiring surgery. The inclusion criteria were fulfilled by 178 patients. The median follow up was 23 months. The Cox model retained the following bad prognostic factors: age less than or equal to 25 years, interval since first symptoms >5 years, interval since previous relapse less than or equal to 6 months, and colonic involvement (p < 0.001). Bootstrapping confirmed the variable selection. Patients were classified into three groups with an increasing risk of relapse (p < 0.001). The worst risk group was composed of patients presenting at least three of the four bad prognostic factors. These results make possible the design of clinical trials in quiescent CD patients with a high risk of relapse.

Published
1995

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