{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T11:01:21Z","timestamp":1793703681660,"version":"4.5.1"},"reference-count":151,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Gastroenterol Hepatol"],"published-print":{"date-parts":[[2024,11]]},"DOI":"10.1038\/s41575-024-00989-y","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T13:02:15Z","timestamp":1728392535000},"page":"792-808","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Interpreting modern randomized controlled trials of medical therapy in inflammatory bowel disease"],"prefix":"10.1038","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4698-9948","authenticated-orcid":false,"given":"Christopher","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G.","family":"Feagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2536-6618","authenticated-orcid":false,"given":"Laurent","family":"Peyrin-Biroulet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7341-1351","authenticated-orcid":false,"given":"Silvio","family":"Danese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5762-5042","authenticated-orcid":false,"given":"Bruce E.","family":"Sands","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remo","family":"Panaccione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"989_CR1","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1056\/NEJM199710093371502","volume":"337","author":"SR Targan","year":"1997","unstructured":"Targan, S. R. et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor \u03b1 for Crohn\u2019s disease. N. Engl. J. Med. 337, 1029\u20131035 (1997).","journal-title":"N. Engl. J. Med."},{"key":"989_CR2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/ecco-jcc\/jjz180","volume":"14","author":"J Torres","year":"2020","unstructured":"Torres, J. et al. ECCO guidelines on therapeutics in Crohn\u2019s disease: medical treatment. J. Crohns Colitis 14, 4\u201322 (2020).","journal-title":"J. Crohns Colitis"},{"key":"989_CR3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/ecco-jcc\/jjab178","volume":"16","author":"T Raine","year":"2022","unstructured":"Raine, T. et al. ECCO guidelines on therapeutics in ulcerative colitis: medical treatment. J. Crohns Colitis 16, 2\u201317 (2022).","journal-title":"J. Crohns Colitis"},{"key":"989_CR4","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/S0140-6736(08)60304-9","volume":"371","author":"G D\u2019Haens","year":"2008","unstructured":"D\u2019Haens, G. et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn\u2019s disease: an open randomised trial. Lancet 371, 660\u2013667 (2008).","journal-title":"Lancet"},{"key":"989_CR5","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/S0140-6736(15)00068-9","volume":"386","author":"R Khanna","year":"2015","unstructured":"Khanna, R. et al. Early combined immunosuppression for the management of Crohn\u2019s disease (REACT): a cluster randomised controlled trial. Lancet 386, 1825\u20131834 (2015).","journal-title":"Lancet"},{"key":"989_CR6","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1056\/NEJMoa0904492","volume":"362","author":"JF Colombel","year":"2010","unstructured":"Colombel, J. F. et al. Infliximab, azathioprine, or combination therapy for Crohn\u2019s disease. N. Engl. J. Med. 362, 1383\u20131395 (2010).","journal-title":"N. Engl. J. Med."},{"key":"989_CR7","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1053\/j.gastro.2013.10.052","volume":"146","author":"R Panaccione","year":"2014","unstructured":"Panaccione, R. et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 146, 392\u2013400.e3 (2014).","journal-title":"Gastroenterology"},{"key":"989_CR8","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1016\/S0140-6736(17)32641-7","volume":"390","author":"JF Colombel","year":"2017","unstructured":"Colombel, J. F. et al. Effect of tight control management on Crohn\u2019s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet 390, 2779\u20132789 (2017).","journal-title":"Lancet"},{"key":"989_CR9","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1606910","volume":"376","author":"WJ Sandborn","year":"2017","unstructured":"Sandborn, W. J. et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 376, 1723\u20131736 (2017).","journal-title":"N. Engl. J. Med."},{"key":"989_CR10","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1016\/S0140-6736(22)00467-6","volume":"399","author":"G D\u2019Haens","year":"2022","unstructured":"D\u2019Haens, G. et al. Risankizumab as induction therapy for Crohn\u2019s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet 399, 2015\u20132030 (2022).","journal-title":"Lancet"},{"key":"989_CR11","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1016\/S0140-6736(22)00581-5","volume":"399","author":"S Danese","year":"2022","unstructured":"Danese, S. et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet 399, 2113\u20132128 (2022).","journal-title":"Lancet"},{"key":"989_CR12","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1016\/S0140-6736(22)00466-4","volume":"399","author":"M Ferrante","year":"2022","unstructured":"Ferrante, M. et al. Risankizumab as maintenance therapy for moderately to severely active Crohn\u2019s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet 399, 2031\u20132046 (2022).","journal-title":"Lancet"},{"key":"989_CR13","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1056\/NEJMoa2212728","volume":"388","author":"EV Loftus Jr.","year":"2023","unstructured":"Loftus, E. V. Jr. et al. Upadacitinib induction and maintenance therapy for Crohn\u2019s disease. N. Engl. J. Med. 388, 1966\u20131980 (2023).","journal-title":"N. Engl. J. Med."},{"key":"989_CR14","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1056\/NEJMoa2033617","volume":"385","author":"WJ Sandborn","year":"2021","unstructured":"Sandborn, W. J. et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 385, 1280\u20131291 (2021).","journal-title":"N. Engl. J. Med."},{"key":"989_CR15","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/S0140-6736(23)00061-2","volume":"401","author":"WJ Sandborn","year":"2023","unstructured":"Sandborn, W. J. et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet 401, 1159\u20131171 (2023).","journal-title":"Lancet"},{"key":"989_CR16","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1056\/NEJMoa1905725","volume":"381","author":"BE Sands","year":"2019","unstructured":"Sands, B. E. et al. Vedolizumab versus adalimumab for moderate-to-severe ulcerative colitis. N. Engl. J. Med. 381, 1215\u20131226 (2019).","journal-title":"N. Engl. J. Med."},{"key":"989_CR17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S2468-1253(21)00294-6","volume":"7","author":"S Danese","year":"2022","unstructured":"Danese, S. et al. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study. Lancet Gastroenterol. Hepatol. 7, 118\u2013127 (2022).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2468-1253(21)00338-1","volume":"7","author":"DT Rubin","year":"2022","unstructured":"Rubin, D. T. et al. Etrolizumab versus adalimumab or placebo as induction therapy for moderately to severely active ulcerative colitis (HIBISCUS): two phase 3 randomised, controlled trials. Lancet Gastroenterol. Hepatol. 7, 17\u201327 (2022).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR19","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S2468-1253(22)00427-7","volume":"8","author":"BG Feagan","year":"2023","unstructured":"Feagan, B. G. et al. Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial. Lancet Gastroenterol. Hepatol. 8, 307\u2013320 (2023).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa2314585","volume":"391","author":"L Peyrin-Biroulet","year":"2024","unstructured":"Peyrin-Biroulet, L. et al. Risankizumab versus ustekinumab for moderate-to-severe Crohn\u2019s disease. N. Engl. J. Med. 391, 213\u2013223 (2024).","journal-title":"N. Engl. J. Med."},{"key":"989_CR21","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1016\/S0140-6736(22)00688-2","volume":"399","author":"BE Sands","year":"2022","unstructured":"Sands, B. E. et al. Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn\u2019s disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial. Lancet 399, 2200\u20132211 (2022).","journal-title":"Lancet"},{"key":"989_CR22","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1093\/ecco-jcc\/jjaa004","volume":"14","author":"KA Wasmann","year":"2020","unstructured":"Wasmann, K. A. et al. Treatment of perianal fistulas in Crohn\u2019s disease, seton versus anti-TNF versus surgical closure following anti-TNF [PISA]: a randomised controlled trial. J. Crohns Colitis 14, 1049\u20131056 (2020).","journal-title":"J. Crohns Colitis"},{"key":"989_CR23","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S2468-1253(22)00088-7","volume":"7","author":"EM Meima-van Praag","year":"2022","unstructured":"Meima-van Praag, E. M. et al. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn\u2019s disease (PISA-II): a patient preference randomised trial. Lancet Gastroenterol. Hepatol. 7, 617\u2013626 (2022).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR24","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S2468-1253(17)30248-0","volume":"2","author":"CY Ponsioen","year":"2017","unstructured":"Ponsioen, C. Y. et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn\u2019s disease: a randomised controlled, open-label, multicentre trial. Lancet Gastroenterol. Hepatol. 2, 785\u2013792 (2017).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR25","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/SLA.0000000000003821","volume":"272","author":"G Luglio","year":"2020","unstructured":"Luglio, G. et al. Surgical prevention of anastomotic recurrence by excluding mesentery in Crohn\u2019s disease: the SuPREMe-CD study \u2013 a randomized clinical trial. Ann. Surg. 272, 210\u2013217 (2020).","journal-title":"Ann. Surg."},{"key":"989_CR26","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1053\/j.gastro.2005.11.030","volume":"130","author":"SB Hanauer","year":"2006","unstructured":"Hanauer, S. B. et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn\u2019s disease: the CLASSIC-I trial. Gastroenterology 130, 323\u2013333 (2006).","journal-title":"Gastroenterology"},{"key":"989_CR27","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1136\/gut.2010.221127","volume":"60","author":"W Reinisch","year":"2011","unstructured":"Reinisch, W. et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut 60, 780\u2013787 (2011).","journal-title":"Gut"},{"key":"989_CR28","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/S0140-6736(02)08512-4","volume":"359","author":"SB Hanauer","year":"2002","unstructured":"Hanauer, S. B. et al. Maintenance infliximab for Crohn\u2019s disease: the ACCENT I randomised trial. Lancet 359, 1541\u20131549 (2002).","journal-title":"Lancet"},{"key":"989_CR29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.gastro.2006.11.041","volume":"132","author":"JF Colombel","year":"2007","unstructured":"Colombel, J. F. et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn\u2019s disease: the CHARM trial. Gastroenterology 132, 52\u201365 (2007).","journal-title":"Gastroenterology"},{"key":"989_CR30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1056\/NEJMoa062897","volume":"357","author":"S Schreiber","year":"2007","unstructured":"Schreiber, S. et al. Maintenance therapy with certolizumab pegol for Crohn\u2019s disease. N. Engl. J. Med. 357, 239\u2013250 (2007).","journal-title":"N. Engl. J. Med."},{"key":"989_CR31","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1053\/j.gastro.2011.10.032","volume":"142","author":"WJ Sandborn","year":"2012","unstructured":"Sandborn, W. J. et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 142, 257\u2013265.e1\u20133 (2012).","journal-title":"Gastroenterology"},{"key":"989_CR32","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1056\/NEJMoa050516","volume":"353","author":"P Rutgeerts","year":"2005","unstructured":"Rutgeerts, P. et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 353, 2462\u20132476 (2005).","journal-title":"N. Engl. J. Med."},{"key":"989_CR33","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1056\/NEJMoa067594","volume":"357","author":"WJ Sandborn","year":"2007","unstructured":"Sandborn, W. J. et al. Certolizumab pegol for the treatment of Crohn\u2019s disease. N. Engl. J. Med. 357, 228\u2013238 (2007).","journal-title":"N. Engl. J. Med."},{"key":"989_CR34","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1215734","volume":"369","author":"BG Feagan","year":"2013","unstructured":"Feagan, B. G. et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 369, 699\u2013710 (2013).","journal-title":"N. Engl. J. Med."},{"key":"989_CR35","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1215739","volume":"369","author":"WJ Sandborn","year":"2013","unstructured":"Sandborn, W. J. et al. Vedolizumab as induction and maintenance therapy for Crohn\u2019s disease. N. Engl. J. Med. 369, 711\u2013721 (2013).","journal-title":"N. Engl. J. Med."},{"key":"989_CR36","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1056\/NEJMoa1602773","volume":"375","author":"BG Feagan","year":"2016","unstructured":"Feagan, B. G. et al. Ustekinumab as induction and maintenance therapy for Crohn\u2019s disease. N. Engl. J. Med. 375, 1946\u20131960 (2016).","journal-title":"N. Engl. J. Med."},{"key":"989_CR37","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1056\/NEJMoa1900750","volume":"381","author":"BE Sands","year":"2019","unstructured":"Sands, B. E. et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 381, 1201\u20131214 (2019).","journal-title":"N. Engl. J. Med."},{"key":"989_CR38","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1097\/MIB.0000000000000909","volume":"22","author":"S Ghosh","year":"2016","unstructured":"Ghosh, S. et al. Interpreting registrational clinical trials of biological therapies in adults with inflammatory bowel diseases. Inflamm. Bowel Dis. 22, 2711\u20132723 (2016).","journal-title":"Inflamm. Bowel Dis."},{"key":"989_CR39","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1093\/ecco-jcc\/jjad020","volume":"17","author":"M Uzzan","year":"2023","unstructured":"Uzzan, M. et al. Declining enrolment and other challenges in IBD clinical trials: causes and potential solutions. J. Crohns Colitis 17, 1066\u20131078 (2023).","journal-title":"J. Crohns Colitis"},{"key":"989_CR40","doi-asserted-by":"crossref","first-page":"otaa023","DOI":"10.1093\/crocol\/otaa023","volume":"2","author":"C Johnson","year":"2020","unstructured":"Johnson, C., Barnes, E. L., Zhang, X. & Long, M. D. Trends and characteristics of clinical trials participation for inflammatory bowel disease in the United States: a report from IBD Partners. Crohns Colitis 2, otaa023 (2020).","journal-title":"Crohns Colitis"},{"key":"989_CR41","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1053\/j.gastro.2019.08.020","volume":"157","author":"MS Harris","year":"2019","unstructured":"Harris, M. S., Wichary, J., Zadnik, M. & Reinisch, W. Competition for clinical trials in inflammatory bowel diseases. Gastroenterology 157, 1457\u20131461.e2 (2019).","journal-title":"Gastroenterology"},{"key":"989_CR42","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1007\/s12325-020-01366-2","volume":"37","author":"WJ Sandborn","year":"2020","unstructured":"Sandborn, W. J. et al. Etrolizumab for the treatment of ulcerative colitis and Crohn\u2019s disease: an overview of the phase 3 clinical program. Adv. Ther. 37, 3417\u20133431 (2020).","journal-title":"Adv. Ther."},{"issue":"Suppl. 1","key":"989_CR43","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/ecco-jcc\/jjy222.441","volume":"13","author":"BE Sands","year":"2019","unstructured":"Sands, B. E. et al. Characterisation of patients with delayed response to ustekinumab for Crohn\u2019s disease [abstract P317]. J. Crohns Colitis 13 (Suppl. 1), 259\u2013260 (2019).","journal-title":"J. Crohns Colitis"},{"issue":"Suppl. 6","key":"989_CR44","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/S0016-5085(23)03526-6","volume":"164","author":"MC Dubinsky","year":"2023","unstructured":"Dubinsky, M. C. et al. Additional risankizumab treatment is effective in patients with moderately to severely active Crohn\u2019s disease who did not achieve cdai clinical response with the initial 12-week induction treatment: results from the advance, motivate, and fortify studies [abstract Tu1710]. Gastroenterology 164 (Suppl. 6), 1088 (2023).","journal-title":"Gastroenterology"},{"issue":"Suppl. 1","key":"989_CR45","doi-asserted-by":"crossref","first-page":"i709","DOI":"10.1093\/ecco-jcc\/jjac190.0712","volume":"17","author":"S Vermeire","year":"2023","unstructured":"Vermeire, S. et al. Efficacy of etrasimod at week 52 among subjects who reached clinical response at week 12: post hoc analysis of the phase 3 ELEVATE UC 52 trial [abstract P582]. J. Crohns Colitis 17 (Suppl. 1), i709\u2013i711 (2023).","journal-title":"J. Crohns Colitis"},{"issue":"Suppl. 1","key":"989_CR46","doi-asserted-by":"crossref","first-page":"i619","DOI":"10.1093\/ecco-jcc\/jjac190.0620","volume":"17","author":"S Vermeire","year":"2023","unstructured":"Vermeire, S. et al. Etrasimod for the treatment of ulcerative colitis: up to 2.5 years of pooled safety data from global clinical trials [abstract P490]. J. Crohns Colitis 17 (Suppl. 1), i619\u2013i620 (2023).","journal-title":"J. Crohns Colitis"},{"key":"989_CR47","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1056\/NEJMoa2207940","volume":"388","author":"G D\u2019Haens","year":"2023","unstructured":"D\u2019Haens, G. et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 388, 2444\u20132455 (2023).","journal-title":"N. Engl. J. Med."},{"key":"989_CR48","unstructured":"US Food and Drug Administration. Demonstrating substantial evidence of effectiveness with one adequate and well-controlled clinical investigation and confirmatory evidence: guidance for industry. FDA www.fda.gov\/media\/172166\/download (2023)."},{"key":"989_CR49","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.jhep.2007.02.015","volume":"46","author":"E Christensen","year":"2007","unstructured":"Christensen, E. Methodology of superiority vs. equivalence trials and non-inferiority trials. J. Hepatol. 46, 947\u2013954 (2007).","journal-title":"J. Hepatol."},{"key":"989_CR50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1590\/s0004-2803.202000000-15","volume":"57","author":"JS Lasa","year":"2020","unstructured":"Lasa, J. S., Zubiaurre, I., Rausch, A. & Olivera, P. Placebo use in the context of inflammatory bowel disease clinical trials. Arq. Gastroenterol. 57, 87\u201390 (2020).","journal-title":"Arq. Gastroenterol."},{"key":"989_CR51","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/ecco-jcc\/jjab140","volume":"16","author":"E Crowley","year":"2022","unstructured":"Crowley, E. et al. Impact of drug approval pathways for paediatric inflammatory bowel disease. J. Crohns Colitis 16, 331\u2013335 (2022).","journal-title":"J. Crohns Colitis"},{"key":"989_CR52","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/ecco-jcc\/jjab194","volume":"16","author":"A Almradi","year":"2022","unstructured":"Almradi, A. et al. Clinical, endoscopic, and safety placebo rates in induction and maintenance trials of Crohn\u2019s disease: meta-analysis of randomised controlled trials. J. Crohns Colitis 16, 717\u2013736 (2022).","journal-title":"J. Crohns Colitis"},{"key":"989_CR53","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.cgh.2022.08.015","volume":"21","author":"ECL Wong","year":"2023","unstructured":"Wong, E. C. L. et al. Predictors of placebo induction response and remission in ulcerative colitis. Clin. Gastroenterol. Hepatol. 21, 1050\u20131060.e9 (2023).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR54","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1093\/ibd\/izac231","volume":"29","author":"ECL Wong","year":"2023","unstructured":"Wong, E. C. L. et al. Predictors of clinical remission to placebo in clinical trials of Crohn\u2019s disease. Inflamm. Bowel Dis. 29, 1390\u20131398 (2023).","journal-title":"Inflamm. Bowel Dis."},{"key":"989_CR55","unstructured":"European Medicines Agency. Guideline on the development of new medicinal products for the treatment of ulcerative colitis \u2013 revision 1. EMA www.ema.europa.eu\/en\/development-new-medicinal-products-treatment-ulcerative-colitis-scientific-guideline (2019)."},{"key":"989_CR56","unstructured":"European Medicines Agency. Clinical investigation of medicinal products for the management of Crohn\u2019s disease \u2013 scientific guideline. EMA www.ema.europa.eu\/en\/clinical-investigation-medicinal-products-management-crohns-disease-scientific-guideline (2018)."},{"key":"989_CR57","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1053\/j.gastro.2019.02.050","volume":"157","author":"C Ma","year":"2019","unstructured":"Ma, C., Guizzetti, L. & Jairath, V. Improving clinical trial efficiency in gastroenterology. Gastroenterology 157, 892\u2013893 (2019).","journal-title":"Gastroenterology"},{"key":"989_CR58","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1053\/j.gastro.2012.08.003","volume":"143","author":"WJ Sandborn","year":"2012","unstructured":"Sandborn, W. J. et al. Once-daily budesonide MMX(R) extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology 143, 1218\u20131226.e12 (2012).","journal-title":"Gastroenterology"},{"key":"989_CR59","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1053\/j.gastro.2022.01.047","volume":"162","author":"WJ Sandborn","year":"2022","unstructured":"Sandborn, W. J. et al. Guselkumab for the treatment of Crohn\u2019s disease: induction results from the phase 2 GALAXI-1 study. Gastroenterology 162, 1650\u20131664l.e8 (2022).","journal-title":"Gastroenterology"},{"key":"989_CR60","first-page":"1057b2","volume":"166","author":"R Panaccione","year":"2024","unstructured":"Panaccione, R. et al. Efficacy and safety of guselkumab therapy in patients with moderately to severely active Crohn\u2019s disease: results of the Galaxi 2 & 3 phase 3 studies. Gastroenterology 166, 1057b2 (2024).","journal-title":"Gastroenterology"},{"issue":"Suppl. 1","key":"989_CR61","doi-asserted-by":"crossref","first-page":"i7","DOI":"10.1093\/ecco-jcc\/jjad212.0005","volume":"18","author":"M Ferrante","year":"2024","unstructured":"Ferrante, M. et al. Primary efficacy and safety of mirikizumab in moderate to severe Crohn\u2019s disease: results of the treat-through VIVID 1 study [abstract OP05]. J. Crohns Colitis 18 (Suppl. 1), i7\u2013i9 (2024).","journal-title":"J. Crohns Colitis"},{"key":"989_CR62","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/ibd\/izz193","volume":"26","author":"J George","year":"2020","unstructured":"George, J. et al. Corticosteroid-free remission vs overall remission in clinical trials of moderate-severe ulcerative colitis and Crohn\u2019s disease. Inflamm. Bowel Dis. 26, 515\u2013523 (2020).","journal-title":"Inflamm. Bowel Dis."},{"key":"989_CR63","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.cgh.2020.12.017","volume":"20","author":"R Khanna","year":"2022","unstructured":"Khanna, R. et al. Endoscopic assessment of inflammatory bowel disease activity in clinical trials. Clin. Gastroenterol. Hepatol. 20, 727\u2013736.e2 (2022).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR64","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/gutjnl-2013-304984","volume":"63","author":"L Peyrin-Biroulet","year":"2014","unstructured":"Peyrin-Biroulet, L. et al. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn\u2019s disease in the SONIC trial. Gut 63, 88\u201395 (2014).","journal-title":"Gut"},{"key":"989_CR65","first-page":"304","volume":"26","author":"JD Lewis","year":"2020","unstructured":"Lewis, J. D. et al. Correlation of stool frequency and abdominal pain measures with simple endoscopic score for Crohn\u2019s disease. Inflamm. Bowel Dis. 26, 304\u2013313 (2020).","journal-title":"Inflamm. Bowel Dis."},{"key":"989_CR66","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1136\/gutjnl-2016-312307","volume":"66","author":"JF Colombel","year":"2017","unstructured":"Colombel, J. F. et al. Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC. Gut 66, 2063\u20132068 (2017).","journal-title":"Gut"},{"key":"989_CR67","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/j.cgh.2019.09.021","volume":"18","author":"C Ma","year":"2020","unstructured":"Ma, C. et al. Discordance between patient-reported outcomes and mucosal inflammation in patients with mild to moderate ulcerative colitis. Clin. Gastroenterol. Hepatol. 18, 1760\u20131768.e1 (2020).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR68","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cgh.2006.11.001","volume":"5","author":"B Yacyshyn","year":"2007","unstructured":"Yacyshyn, B. et al. A randomized, double-masked, placebo-controlled study of alicaforsen, an antisense inhibitor of intercellular adhesion molecule 1, for the treatment of subjects with active Crohn\u2019s disease. Clin. Gastroenterol. Hepatol. 5, 215\u2013220 (2007).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR69","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1136\/gutjnl-2016-312735","volume":"66","author":"J Panes","year":"2017","unstructured":"Panes, J. et al. Tofacitinib for induction and maintenance therapy of Crohn\u2019s disease: results of two phase IIb randomised placebo-controlled trials. Gut 66, 1049\u20131059 (2017).","journal-title":"Gut"},{"key":"989_CR70","first-page":"418","volume":"70","author":"K Gottlieb","year":"2021","unstructured":"Gottlieb, K. et al. Endoscopy and central reading in inflammatory bowel disease clinical trials: achievements, challenges and future developments. Gut 70, 418\u2013426 (2021).","journal-title":"Gut"},{"key":"989_CR71","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1053\/j.gastro.2013.03.025","volume":"145","author":"BG Feagan","year":"2013","unstructured":"Feagan, B. G. et al. The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis. Gastroenterology 145, 149\u2013157.e2 (2013).","journal-title":"Gastroenterology"},{"key":"989_CR72","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/ibd\/izad052","volume":"30","author":"SK Vuyyuru","year":"2023","unstructured":"Vuyyuru, S. K. et al. Endoscopic and histological placebo rates in Crohn\u2019s disease clinical trials: a systematic review and meta-analysis. Inflamm. Bowel Dis. 30, 651\u2013659 (2023).","journal-title":"Inflamm. Bowel Dis."},{"key":"989_CR73","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/ecco-jcc\/jjab135","volume":"16","author":"R Sedano","year":"2022","unstructured":"Sedano, R. et al. Systematic review and meta-analysis: clinical, endoscopic, histological and safety placebo rates in induction and maintenance trials of ulcerative colitis. J. Crohns Colitis 16, 224\u2013243 (2022).","journal-title":"J. Crohns Colitis"},{"key":"989_CR74","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.gie.2020.05.020","volume":"93","author":"W Reinisch","year":"2021","unstructured":"Reinisch, W. et al. Impact of various central endoscopy reading models on treatment outcome in Crohn\u2019s disease using data from the randomized, controlled, exploratory cohort arm of the BERGAMOT trial. Gastrointest. Endosc. 93, 174\u2013182.e2 (2021).","journal-title":"Gastrointest. Endosc."},{"key":"989_CR75","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1053\/j.gastro.2005.06.064","volume":"129","author":"S Schreiber","year":"2005","unstructured":"Schreiber, S. et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn\u2019s disease. Gastroenterology 129, 807\u2013818 (2005).","journal-title":"Gastroenterology"},{"issue":"Suppl. 8","key":"989_CR76","first-page":"89","volume":"10","author":"V Jairath","year":"2022","unstructured":"Jairath, V. et al. A cluster-randomised controlled trial of an enhanced treatment algorithm for the management of Crohn\u2019s disease: React-2 [abstract OP110]. United Eur. Gastroenterol. J. 10 (Suppl. 8), 89 (2022).","journal-title":"United Eur. Gastroenterol. J."},{"key":"989_CR77","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.cgh.2012.02.004","volume":"10","author":"C Ha","year":"2012","unstructured":"Ha, C., Ullman, T. A., Siegel, C. A. & Kornbluth, A. Patients enrolled in randomized controlled trials do not represent the inflammatory bowel disease patient population. Clin. Gastroenterol. Hepatol. 10, 1002\u20131007 (2012).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR78","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1053\/j.gastro.2021.09.054","volume":"162","author":"R Sedano","year":"2022","unstructured":"Sedano, R. et al. Underrepresentation of minorities and underreporting of race and ethnicity in Crohn\u2019s disease clinical trials. Gastroenterology 162, 338\u2013340.e2 (2022).","journal-title":"Gastroenterology"},{"key":"989_CR79","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1053\/j.gastro.2021.09.035","volume":"162","author":"NA Cohen","year":"2022","unstructured":"Cohen, N. A., Silfen, A. & Rubin, D. T. Inclusion of under-represented racial and ethnic minorities in randomized clinical trials for inflammatory bowel disease. Gastroenterology 162, 17\u201321 (2022).","journal-title":"Gastroenterology"},{"key":"989_CR80","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1053\/j.gastro.2020.08.064","volume":"160","author":"EL Barnes","year":"2021","unstructured":"Barnes, E. L., Loftus, E. V. Jr. & Kappelman, M. D. Effects of race and ethnicity on diagnosis and management of inflammatory bowel diseases. Gastroenterology 160, 677\u2013689 (2021).","journal-title":"Gastroenterology"},{"key":"989_CR81","doi-asserted-by":"crossref","first-page":"8309","DOI":"10.2147\/OTT.S177007","volume":"11","author":"Y Liu","year":"2018","unstructured":"Liu, Y. et al. Associations between the NUDT15 R139C polymorphism and susceptibility to thiopurine-induced leukopenia in Asians: a meta-analysis. Onco Targets Ther. 11, 8309\u20138317 (2018).","journal-title":"Onco Targets Ther."},{"key":"989_CR82","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1002\/art.38745","volume":"66","author":"KL Winthrop","year":"2014","unstructured":"Winthrop, K. L. et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol. 66, 2675\u20132684 (2014).","journal-title":"Arthritis Rheumatol."},{"key":"989_CR83","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2468-1253(19)30333-4","volume":"5","author":"GBD 2017 Inflammatory Bowel Disease Collaborators","year":"2020","unstructured":"GBD 2017 Inflammatory Bowel Disease Collaborators The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 5, 17\u201330 (2020).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR84","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1053\/j.gastro.2021.10.037","volume":"162","author":"S Ben-Horin","year":"2022","unstructured":"Ben-Horin, S. et al. Efficacy of biologic drugs in short-duration versus long-duration inflammatory bowel disease: a systematic review and an individual-patient data meta-analysis of randomized controlled trials. Gastroenterology 162, 482\u2013494 (2022).","journal-title":"Gastroenterology"},{"key":"989_CR85","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.gastro.2014.09.015","volume":"148","author":"B Pariente","year":"2015","unstructured":"Pariente, B. et al. Development of the Lemann index to assess digestive tract damage in patients with Crohn\u2019s disease. Gastroenterology 148, 52\u201363.e3 (2015).","journal-title":"Gastroenterology"},{"key":"989_CR86","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.2174\/1389450115666140908125738","volume":"15","author":"S Danese","year":"2014","unstructured":"Danese, S., Fiorino, G., Fernandes, C. & Peyrin-Biroulet, L. Catching the therapeutic window of opportunity in early Crohn\u2019s disease. Curr. Drug. Targets 15, 1056\u20131063 (2014).","journal-title":"Curr. Drug. Targets"},{"key":"989_CR87","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1093\/ecco-jcc\/jjad106","volume":"17","author":"J Burisch","year":"2023","unstructured":"Burisch, J., Safroneeva, E., Laoun, R. & Ma, C. Lack of benefit for early escalation to advanced therapies in ulcerative colitis: critical appraisal of current evidence. J. Crohns Colitis 17, 2002\u20132011 (2023).","journal-title":"J. Crohns Colitis"},{"key":"989_CR88","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/S2468-1253(21)00312-5","volume":"6","author":"S Singh","year":"2021","unstructured":"Singh, S. et al. Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn\u2019s disease: a systematic review and network meta-analysis. Lancet Gastroenterol. Hepatol. 6, 1002\u20131014 (2021).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR89","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S2468-1253(21)00377-0","volume":"7","author":"JS Lasa","year":"2022","unstructured":"Lasa, J. S., Olivera, P. A., Danese, S. & Peyrin-Biroulet, L. Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis. Lancet Gastroenterol. Hepatol. 7, 161\u2013170 (2022).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR90","unstructured":"US Food and Drug Administration. Guidance document. Ulcerative colitis: developing drugs for treatment. FDA www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/ulcerative-colitis-developing-drugs-treatment (2022)."},{"key":"989_CR91","unstructured":"US Food and Drug Administration. Guidance document. Crohn\u2019s disease: developing drugs for treatment. FDA www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/crohns-disease-developing-drugs-treatment (2022)."},{"key":"989_CR92","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/ajg.2011.103","volume":"106","author":"H Yanai","year":"2011","unstructured":"Yanai, H. & Hanauer, S. B. Assessing response and loss of response to biological therapies in IBD. Am. J. Gastroenterol. 106, 685\u2013698 (2011).","journal-title":"Am. J. Gastroenterol."},{"key":"989_CR93","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1056\/NEJMoa2208450","volume":"388","author":"S Travis","year":"2023","unstructured":"Travis, S. et al. Vedolizumab for the treatment of chronic pouchitis. N. Engl. J. Med. 388, 1191\u20131200 (2023).","journal-title":"N. Engl. J. Med."},{"key":"989_CR94","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/ibd\/izab259","volume":"28","author":"J Hanzel","year":"2022","unstructured":"Hanzel, J. et al. Recommendations for standardizing clinical trial design and endoscopic assessment in postoperative Crohn\u2019s disease. Inflamm. Bowel Dis. 28, 1321\u20131331 (2022).","journal-title":"Inflamm. Bowel Dis."},{"key":"989_CR95","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1136\/gutjnl-2017-314918","volume":"67","author":"PG Kotze","year":"2018","unstructured":"Kotze, P. G. et al. Modern management of perianal fistulas in Crohn\u2019s disease: future directions. Gut 67, 1181\u20131194 (2018).","journal-title":"Gut"},{"key":"989_CR96","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1053\/j.gastro.2019.07.027","volume":"157","author":"P Hindryckx","year":"2019","unstructured":"Hindryckx, P. et al. Development and validation of a magnetic resonance index for assessing fistulas in patients with Crohn\u2019s disease. Gastroenterology 157, 1233\u20131244.e5 (2019).","journal-title":"Gastroenterology"},{"key":"989_CR97","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.14309\/ajg.0000000000002215","volume":"118","author":"SK Vuyyuru","year":"2023","unstructured":"Vuyyuru, S. K. et al. Patients with Crohn\u2019s disease and permanent ileostomy are universally excluded from clinical trials: a systematic review. Am. J. Gastroenterol. 118, 1285\u20131288 (2023).","journal-title":"Am. J. Gastroenterol."},{"key":"989_CR98","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1136\/gutjnl-2012-304353","volume":"62","author":"F Rieder","year":"2013","unstructured":"Rieder, F., Zimmermann, E. M., Remzi, F. H. & Sandborn, W. J. Crohn\u2019s disease complicated by strictures: a systematic review. Gut 62, 1072\u20131084 (2013).","journal-title":"Gut"},{"key":"989_CR99","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/apt.14853","volume":"48","author":"F Rieder","year":"2018","unstructured":"Rieder, F. et al. An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn\u2019s disease. Aliment. Pharmacol. Ther. 48, 347\u2013357 (2018).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"989_CR100","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1136\/gutjnl-2018-318081","volume":"68","author":"D Bettenworth","year":"2019","unstructured":"Bettenworth, D. et al. Assessment of Crohn\u2019s disease-associated small bowel strictures and fibrosis on cross-sectional imaging: a systematic review. Gut 68, 1115\u20131126 (2019).","journal-title":"Gut"},{"key":"989_CR101","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1053\/j.gastro.2022.02.036","volume":"162","author":"J Hanzel","year":"2022","unstructured":"Hanzel, J., Ma, C. & Jairath, V. Design of clinical trials for mild to moderate Crohn\u2019s disease. Gastroenterology 162, 1800\u20131814.e1 (2022).","journal-title":"Gastroenterology"},{"key":"989_CR102","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1053\/j.gastro.2021.12.284","volume":"162","author":"R Sedano","year":"2022","unstructured":"Sedano, R., Jairath, V. & Ma, C. Design of clinical trials for mild to moderate ulcerative colitis. Gastroenterology 162, 1005\u20131018 (2022).","journal-title":"Gastroenterology"},{"key":"989_CR103","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/j.cgh.2018.02.051","volume":"16","author":"C Ma","year":"2018","unstructured":"Ma, C. et al. Heterogeneity in definitions of efficacy and safety endpoints for clinical trials of Crohn\u2019s disease: a systematic review. Clin. Gastroenterol. Hepatol. 16, 1407\u20131419.e22 (2018).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR104","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.cgh.2017.08.025","volume":"16","author":"C Ma","year":"2018","unstructured":"Ma, C. et al. Heterogeneity in definitions of endpoints for clinical trials of ulcerative colitis: a systematic review for development of a core outcome set. Clin. Gastroenterol. Hepatol. 16, 637\u2013647.e13 (2018).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR105","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1111\/apt.13408","volume":"42","author":"V Jairath","year":"2015","unstructured":"Jairath, V. et al. Development of interim patient-reported outcome measures for the assessment of ulcerative colitis disease activity in clinical trials. Aliment. Pharmacol. Ther. 42, 1200\u20131210 (2015).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"989_CR106","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/apt.13001","volume":"41","author":"R Khanna","year":"2015","unstructured":"Khanna, R. et al. A retrospective analysis: the development of patient reported outcome measures for the assessment of Crohn\u2019s disease activity. Aliment. Pharmacol. Ther. 41, 77\u201386 (2015).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"989_CR107","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s41687-022-00439-w","volume":"6","author":"MC Dubinsky","year":"2022","unstructured":"Dubinsky, M. C. et al. Incorporating patient experience into drug development for ulcerative colitis: development of the Urgency Numeric Rating Scale, a patient-reported outcome measure to assess bowel urgency in adults. J. Patient Rep. Outcomes 6, 31 (2022).","journal-title":"J. Patient Rep. Outcomes"},{"key":"989_CR108","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0016-5107(04)01878-4","volume":"60","author":"M Daperno","year":"2004","unstructured":"Daperno, M. et al. Development and validation of a new, simplified endoscopic activity score for Crohn\u2019s disease: the SES-CD. Gastrointest. Endosc. 60, 505\u2013512 (2004).","journal-title":"Gastrointest. Endosc."},{"key":"989_CR109","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.14309\/ajg.0000000000001795","volume":"117","author":"N Narula","year":"2022","unstructured":"Narula, N. et al. Comparative effectiveness of biologics for endoscopic healing of the ileum and colon in Crohn\u2019s disease. Am. J. Gastroenterol. 117, 1106\u20131117 (2022).","journal-title":"Am. J. Gastroenterol."},{"issue":"Suppl. 1","key":"989_CR110","doi-asserted-by":"crossref","first-page":"i381","DOI":"10.1093\/ecco-jcc\/jjab232.507","volume":"16","author":"BG Feagan","year":"2022","unstructured":"Feagan, B. G. et al. Early improvement of endoscopic outcomes with risankizumab is associated with reduced hospitalisation and surgery rates in patients with Crohn\u2019s disease [abstract P380]. J. Crohns Colitis 16 (Suppl. 1), i381\u2013i382 (2022).","journal-title":"J. Crohns Colitis"},{"key":"989_CR111","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1136\/gutjnl-2021-324658","volume":"71","author":"C Ma","year":"2022","unstructured":"Ma, C. et al. Methods for handling missing segments in Crohn\u2019s disease clinical trials: analysis from the EXTEND trial. Gut 71, 447\u2013448 (2022).","journal-title":"Gut"},{"key":"989_CR112","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S2468-1253(21)00096-0","volume":"6","author":"S Geyl","year":"2021","unstructured":"Geyl, S. et al. Transmural healing as a therapeutic goal in Crohn\u2019s disease: a systematic review. Lancet Gastroenterol. Hepatol. 6, 659\u2013667 (2021).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR113","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1111\/apt.16288","volume":"53","author":"TM Goodsall","year":"2021","unstructured":"Goodsall, T. M. et al. Standardisation of intestinal ultrasound scoring in clinical trials for luminal Crohn\u2019s disease. Aliment. Pharmacol. Ther. 53, 873\u2013886 (2021).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"989_CR114","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S2468-1253(21)00474-X","volume":"7","author":"S Danese","year":"2022","unstructured":"Danese, S. et al. Treat to target versus standard of care for patients with Crohn\u2019s disease treated with ustekinumab (STARDUST): an open-label, multicentre, randomised phase 3b trial. Lancet Gastroenterol. Hepatol. 7, 294\u2013306 (2022).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR115","doi-asserted-by":"crossref","first-page":"otab007","DOI":"10.1093\/crocol\/otab007","volume":"3","author":"AN Naegeli","year":"2021","unstructured":"Naegeli, A. N. et al. Full, partial, and modified permutations of the Mayo score: characterizing clinical and patient-reported outcomes in ulcerative colitis patients. Crohns Colitis 3, otab007 (2021).","journal-title":"Crohns Colitis"},{"key":"989_CR116","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1056\/NEJM198712243172603","volume":"317","author":"KW Schroeder","year":"1987","unstructured":"Schroeder, K. W., Tremaine, W. J. & Ilstrup, D. M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N. Engl. J. Med. 317, 1625\u20131629 (1987).","journal-title":"N. Engl. J. Med."},{"key":"989_CR117","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/ajg.2009.83","volume":"104","author":"EJ Scherl","year":"2009","unstructured":"Scherl, E. J. et al. Safety and efficacy of a new 3.3 g b.i.d. tablet formulation in patients with mild-to-moderately-active ulcerative colitis: a multicenter, randomized, double-blind, placebo-controlled study. Am. J. Gastroenterol. 104, 1452\u20131459 (2009).","journal-title":"Am. J. Gastroenterol."},{"key":"989_CR118","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1053\/j.gastro.2022.06.068","volume":"163","author":"The CORE-IBD Collaborators","year":"2022","unstructured":"The CORE-IBD Collaborators et al.CORE-IBD: a multidisciplinary international consensus initiative to develop a core outcome set for randomized controlled trials in inflammatory bowel disease. Gastroenterology 163, 950\u2013964 (2022).","journal-title":"Gastroenterology"},{"key":"989_CR119","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1053\/j.gastro.2013.07.024","volume":"145","author":"SP Travis","year":"2013","unstructured":"Travis, S. P. et al. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology 145, 987\u2013995 (2013).","journal-title":"Gastroenterology"},{"key":"989_CR120","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1136\/gutjnl-2011-300486","volume":"61","author":"SP Travis","year":"2012","unstructured":"Travis, S. P. et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut 61, 535\u2013542 (2012).","journal-title":"Gut"},{"key":"989_CR121","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/jnci\/95.3.230","volume":"95","author":"NM Gatto","year":"2003","unstructured":"Gatto, N. M. et al. Risk of perforation after colonoscopy and sigmoidoscopy: a population-based study. J. Natl Cancer Inst. 95, 230\u2013236 (2003).","journal-title":"J. Natl Cancer Inst."},{"key":"989_CR122","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1053\/j.gastro.2015.10.016","volume":"150","author":"JF Colombel","year":"2016","unstructured":"Colombel, J. F. et al. Agreement between rectosigmoidoscopy and colonoscopy analyses of disease activity and healing in patients with ulcerative colitis. Gastroenterology 150, 389\u2013395.e3 (2016).","journal-title":"Gastroenterology"},{"key":"989_CR123","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1093\/ecco-jcc\/jjaa110","volume":"14","author":"F Magro","year":"2020","unstructured":"Magro, F. et al. ECCO position paper: harmonization of the approach to ulcerative colitis histopathology. J. Crohns Colitis 14, 1503\u20131511 (2020).","journal-title":"J. Crohns Colitis"},{"key":"989_CR124","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1053\/j.gastro.2021.02.035","volume":"160","author":"C Ma","year":"2021","unstructured":"Ma, C. et al. An international consensus to standardize integration of histopathology in ulcerative colitis clinical trials. Gastroenterology 160, 2291\u20132302 (2021).","journal-title":"Gastroenterology"},{"key":"989_CR125","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1136\/gutjnl-2015-310393","volume":"66","author":"MH Mosli","year":"2017","unstructured":"Mosli, M. H. et al. Development and validation of a histological index for UC. Gut 66, 50\u201358 (2017).","journal-title":"Gut"},{"key":"989_CR126","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/gutjnl-2015-310187","volume":"66","author":"A Marchal-Bressenot","year":"2017","unstructured":"Marchal-Bressenot, A. et al. Development and validation of the Nancy histological index for UC. Gut 66, 43\u201349 (2017).","journal-title":"Gut"},{"key":"989_CR127","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1136\/gut.47.3.404","volume":"47","author":"K Geboes","year":"2000","unstructured":"Geboes, K. et al. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut 47, 404\u2013409 (2000).","journal-title":"Gut"},{"key":"989_CR128","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1093\/ecco-jcc\/jjad087","volume":"17","author":"L Peyrin-Biroulet","year":"2023","unstructured":"Peyrin-Biroulet, L. et al. A comparative evaluation of the measurement properties of three histological indices of mucosal healing in ulcerative colitis: Geboes Score, Robarts Histopathology Index, and Nancy Index. J. Crohns Colitis 17, 1733\u20131743 (2023).","journal-title":"J. Crohns Colitis"},{"key":"989_CR129","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1053\/j.gastro.2020.06.043","volume":"159","author":"H Yoon","year":"2020","unstructured":"Yoon, H. et al. Incremental benefit of achieving endoscopic and histologic remission in patients with ulcerative colitis: a systematic review and meta-analysis. Gastroenterology 159, 1262\u20131275.e7 (2020).","journal-title":"Gastroenterology"},{"key":"989_CR130","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1056\/NEJMoa2109927","volume":"386","author":"SR Ytterberg","year":"2022","unstructured":"Ytterberg, S. R. et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N. Engl. J. Med. 386, 316\u2013326 (2022).","journal-title":"N. Engl. J. Med."},{"key":"989_CR131","unstructured":"US Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. FDA www.fda.gov\/drugs\/drug-safety-and-availability\/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death (2021)."},{"key":"989_CR132","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/ecco-jcc\/jjac141","volume":"17","author":"WJ Sandborn","year":"2023","unstructured":"Sandborn, W. J. et al. Tofacitinib for the treatment of ulcerative colitis: an integrated summary of up to 7.8 years of safety data from the global clinical programme. J. Crohns Colitis 17, 338\u2013351 (2023).","journal-title":"J. Crohns Colitis"},{"key":"989_CR133","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/ueg2.12584","volume":"12","author":"J Pan\u00e9s","year":"2024","unstructured":"Pan\u00e9s, J. et al. Analysis of tofacitinib safety in ulcerative colitis from the completed global clinical developmental program up to 9.2 years of drug exposure. United Eur. Gastroenterol. J. 12, 793\u2013801 (2024).","journal-title":"United Eur. Gastroenterol. J."},{"key":"989_CR134","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1016\/S0140-6736(21)00666-8","volume":"397","author":"BG Feagan","year":"2021","unstructured":"Feagan, B. G. et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b\/3 double-blind, randomised, placebo-controlled trial. Lancet 397, 2372\u20132384 (2021).","journal-title":"Lancet"},{"key":"989_CR135","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1136\/ard-2023-224482","volume":"82","author":"R Fleischmann","year":"2023","unstructured":"Fleischmann, R. et al. Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme. Ann. Rheum. Dis. 82, 1130\u20131141 (2023).","journal-title":"Ann. Rheum. Dis."},{"key":"989_CR136","unstructured":"European Medicines Agency. EMA recommends measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. EMA www.ema.europa.eu\/en\/news\/ema-recommends-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic-inflammatory-disorders (2022)."},{"key":"989_CR137","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/MIB.0000000000000907","volume":"23","author":"HH Herfarth","year":"2017","unstructured":"Herfarth, H. H. et al. Investigator-initiated IBD trials in the United States: facts, obstacles, and answers. Inflamm. Bowel Dis. 23, 14\u201322 (2017).","journal-title":"Inflamm. Bowel Dis."},{"key":"989_CR138","doi-asserted-by":"crossref","first-page":"EVIDoa2200061","DOI":"10.1056\/EVIDoa2200061","volume":"1","author":"S Buhl","year":"2022","unstructured":"Buhl, S. et al. Discontinuation of infliximab therapy in patients with Crohn\u2019s disease. NEJM Evid. 1, EVIDoa2200061 (2022).","journal-title":"NEJM Evid."},{"key":"989_CR139","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S2468-1253(22)00385-5","volume":"8","author":"E Louis","year":"2023","unstructured":"Louis, E. et al. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn\u2019s disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol. Hepatol. 8, 215\u2013227 (2023).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR140","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S2468-1253(24)00034-7","volume":"9","author":"NM Noor","year":"2024","unstructured":"Noor, N. M. et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn\u2019s disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol. Hepatol. 9, 415\u2013427 (2024).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR141","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1093\/ecco-jcc\/jjae026","volume":"18","author":"MC Fantini","year":"2024","unstructured":"Fantini, M. C. et al. Pragmatic trial design to compare real-world effectiveness of different treatments for inflammatory bowel diseases: the PRACTICE-IBD European consensus. J. Crohns Colitis 18, 1222\u20131231 (2024).","journal-title":"J. Crohns Colitis"},{"key":"989_CR142","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S2468-1253(16)30003-6","volume":"1","author":"JG Williams","year":"2016","unstructured":"Williams, J. G. et al. Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomised trial. Lancet Gastroenterol. Hepatol. 1, 15\u201324 (2016).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"989_CR143","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S2468-1253(22)00434-4","volume":"8","author":"RCA van Linschoten","year":"2023","unstructured":"van Linschoten, R. C. A. et al. Increased versus conventional adalimumab dose interval for patients with Crohn\u2019s disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial. Lancet Gastroenterol. Hepatol. 8, 343\u2013355 (2023).","journal-title":"Lancet Gastroenterol. Hepatol."},{"issue":"Suppl. 1","key":"989_CR144","doi-asserted-by":"crossref","first-page":"i62","DOI":"10.1093\/ecco-jcc\/jjad212.0035","volume":"18","author":"V Jairath","year":"2024","unstructured":"Jairath, V. et al. Efficacy of mirikizumab in comparison to ustekinumab in patients with moderate to severe Crohn\u2019s disease: results from the phase 3 VIVID 1 study [abstract OP35]. J. Crohns Colitis 18 (Suppl. 1), i62\u2013i64 (2024).","journal-title":"J. Crohns Colitis"},{"key":"989_CR145","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1053\/j.gastro.2021.03.065","volume":"161","author":"MC Dubinsky","year":"2021","unstructured":"Dubinsky, M. C., Collins, R. & Abreu, M. T. International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) Challenges and opportunities in IBD clinical trial design. Gastroenterology 161, 400\u2013404 (2021).","journal-title":"Gastroenterology"},{"key":"989_CR146","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1136\/gutjnl-2011-301668","volume":"61","author":"W Hueber","year":"2012","unstructured":"Hueber, W. et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn\u2019s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 61, 1693\u20131700 (2012).","journal-title":"Gut"},{"key":"989_CR147","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/j.cgh.2023.09.010","volume":"22","author":"JF Colombel","year":"2023","unstructured":"Colombel, J. F. et al. Vedolizumab, adalimumab, and methotrexate combination therapy in Crohn\u2019s disease (EXPLORER). Clin. Gastroenterol. Hepatol. 22, 1487\u20131496.e12 (2023).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR148","doi-asserted-by":"crossref","DOI":"10.1186\/s12916-018-1017-7","volume":"16","author":"P Pallmann","year":"2018","unstructured":"Pallmann, P. et al. Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Med. 16, 29 (2018).","journal-title":"BMC Med."},{"key":"989_CR149","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1056\/NEJMra1510062","volume":"377","author":"J Woodcock","year":"2017","unstructured":"Woodcock, J. & LaVange, L. M. Master protocols to study multiple therapies, multiple diseases, or both. N. Engl. J. Med. 377, 62\u201370 (2017).","journal-title":"N. Engl. J. Med."},{"key":"989_CR150","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1016\/j.cgh.2022.12.029","volume":"21","author":"WJ Sandborn","year":"2023","unstructured":"Sandborn, W. J. et al. Oral ritlecitinib and brepocitinib for moderate-to-severe ulcerative colitis: results from a randomized, phase 2b study. Clin. Gastroenterol. Hepatol. 21, 2616\u20132628.e7 (2023).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"989_CR151","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1053\/j.gastro.2020.10.065","volume":"160","author":"C Le Berre","year":"2021","unstructured":"Le Berre, C. & Peyrin-Biroulet, L. Selecting end points for disease-modification trials in inflammatory bowel disease: the SPIRIT consensus from the IOIBD. Gastroenterology 160, 1452\u20131460.e21 (2021).","journal-title":"Gastroenterology"}],"container-title":["Nature Reviews Gastroenterology &amp; Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41575-024-00989-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41575-024-00989-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41575-024-00989-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T13:08:54Z","timestamp":1729861734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41575-024-00989-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":151,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["989"],"URL":"https:\/\/doi.org\/10.1038\/s41575-024-00989-y","relation":{},"ISSN":["1759-5045","1759-5053"],"issn-type":[{"value":"1759-5045","type":"print"},{"value":"1759-5053","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,8]]},"assertion":[{"value":"3 September 2024","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2024","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.M. has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol-Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda and Tillotts Pharma; speaker\u2019s fees from AbbVie, Amgen, AVIR Pharma Inc., Alimentiv, Bristol-Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi and Takeda; royalties from Springer Publishing; and research support from AbbVie, Ferring and Pfizer. V.J. has received consulting\/advisory board fees from AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol-Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Sorriso, Takeda, TD Securities, Teva, Topivert, Ventyx and Vividion; and speaker\u2019s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda and Fresenius Kabi. B.G.F. is a scientific advisory board member for AbbVie, Allergan, Amgen, AstraZeneca, Avaxia Biologics Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Elan, Biogen, Ferring, Genentech-Roche, Janssen\u2013Johnson & Johnson, Merck, Millennium, Nestl\u00e9, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos, Salix, Sigmoid Pharma, Takeda, Teva, TiGenix, Tillotts Pharma and UCB Pharma; has received consulting fees from AbbVie, Actogenix, Akros, Albireo Pharma, Allergan, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan-Biogen, EnGene, Ferring, Genentech-Roche, GiCare Pharma, Gilead Sciences, Given Imaging, GlaxoSmithKline, Ironwood, Janssen Biotech-Centocor, Janssen\u2013Johnson & Johnson, Kyowa Hakko Kirin, Eli Lilly, Merck, Mesoblast Pharma, Millennium, Nestl\u00e9, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos Salix, Sanofi, Shire, Sigmoid Pharma, Synergy Pharma, Takeda, Teva, TiGenix, Tillotts Pharma, UCB Pharma, Vertex, VHsquared, Wyeth, Zealand and Zygenia; has received lecture fees from AbbVie, Janssen\u2013Johnson & Johnson, Takeda and UCB Pharma; has received grant support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech-Centocor, Janssen-Johnson & Johnson, Pfizer, Receptos, Sanofi and Takeda; and is the Senior Scientific Officer of Alimentiv Inc. L.P.-B. has received personal fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par\u2019Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant and Vectivbio. S.D. reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen-Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial and Vifor; and reports lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer and Takeda. B.E.S. has served as a consultant or received speaker\u2019s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celltrion, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead Sciences, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen\u2013Johnson & Johnson, Kaleido, Kalyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences and Viela Bio; and had stock options from Ventyx Biosciences. R.P. has served as a consultant for Abbott, AbbVie, Abbivax, Alimentiv Inc. (formerly Robarts Clinical Trials), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx and UCB; received speaker\u2019s fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; and served on advisory boards for AbbVie, Alimentiv Inc. (formerly Robarts Clinical Trials), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals and Ventyx.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}