{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T22:59:39Z","timestamp":1772405979108,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>With the increasing number of effective therapies for inflammatory bowel diseases (IBD), determining optimal treatment sequences is challenging. Given the impracticality of conducting randomized head-to-head trials for every comparison, this study assessed whether phase 3 placebo-controlled trials can reliably predict outcomes of published head-to-head studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three randomized head-to-head trials without placebo arms were analyzed alongside their corresponding phase 3 placebo-controlled trials. Effect sizes for clinical and endoscopic endpoints were extracted for comparison.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the VARSITY trial, vedolizumab achieved an 8.8% higher clinical remission rate than adalimumab at week 52 in patients with ulcerative colitis. Placebo-controlled studies estimated a 17.3% advantage for vedolizumab; however, differences in trial design and patient populations between GEMINI-1 and ULTRA-2 limited the robustness of this indirect comparison. In Crohn\u2019s disease, indirect comparisons of IM-UNITI, CLASSIC-II, and CHARM suggested an 11.6%-18.6% higher efficacy for adalimumab compared with ustekinumab in biologic-na\u00efve patients, yet the SEAVUE head-to-head trial found no significant difference at week 52. Most recently, the SEQUENCE trial demonstrated a +15.6% superiority of risankizumab over ustekinumab in endoscopic remission at week 48 among bio-exposed Crohn\u2019s disease patients, whereas indirect comparisons between FORTIFY and IM-UNITI were confounded by clinically relevant population differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Significant heterogeneity in trial design, populations, and outcome reporting limits the predictive value of placebo-controlled trials. Randomized head-to-head trials remain essential for optimizing IBD therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjag009","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T10:17:43Z","timestamp":1769422663000},"source":"Crossref","is-referenced-by-count":1,"title":["A descriptive comparison of phase 3 results and head-to-head trials in inflammatory bowel diseases"],"prefix":"10.1093","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3222-0529","authenticated-orcid":false,"given":"Zlata","family":"Chkolnaia","sequence":"first","affiliation":[{"name":"Gastroenterology Department, Henri Mondor Hospital, Paris Est Cr\u00e9teil University UPEC, Assistance Publique-H\u00f4pitaux de Paris (AP-HP) , Cr\u00e9teil, 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