Clinical Trial Design in Ulcerative Colitis: Interpreting Evolving Endpoints Based on Post Hoc Analyses of the Vedolizumab Phase 3 Trials GEMINI 1 and VISIBLE 1.

Autor:	Sandborn WJ; Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA., Sands BE; Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Uddin S; Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA, USA., Qasim Khan RM; Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA, USA., Sagar Mukherjee R; Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA, USA.
Jazyk:	angličtina
Zdroj:	Crohn's & colitis 360 [Crohns Colitis 360] 2023 Dec 18; Vol. 6 (1), pp. otad076. Date of Electronic Publication: 2023 Dec 18 (Print Publication: 2024).
DOI:	10.1093/crocol/otad076
Abstrakt:	Background: The 12-point total Mayo score including a Physician's Global Assessment (PGA) of disease activity has been used to assess outcomes in clinical trials for ulcerative colitis (UC). In 2016, the US Food and Drug Administration (FDA) issued guidance advising the removal of the PGA in future trials. We examined how endpoints in UC trials have evolved and conducted a post hoc analysis of the GEMINI 1 and VISIBLE 1 trials to understand how the use of a 9-point modified Mayo score, excluding PGA, compares with the total Mayo score. Methods: Endpoint definitions of clinical remission in phase 3 trials were extracted from published literature and ClinicalTrials.gov. The difference (%Δ) between the proportions of patients in GEMINI 1 and VISIBLE 1 achieving clinical remission with vedolizumab versus placebo at week 52 was measured according to 4 endpoint definitions. Results: Trials completed up to the end of 2019 used the total Mayo score to assess clinical remission. Most trials that were completed or estimated to be completed by June 2020 or later used modified Mayo scores. Post hoc analysis revealed decreasing endpoint stringency was associated with increasing %Δ values. The modified Mayo score definition most like the definition recommended by the FDA produced %Δ values like those reported using the total Mayo score in GEMINI 1 and VISIBLE 1. Conclusions: Endpoint definitions for UC clinical trials have evolved following FDA guidance. The efficacy of vedolizumab, measured using modified Mayo scoring, was comparable to values reported using the total Mayo score. Competing Interests: W.J.S. has received consulting fees from AbbVie, Abivax, Alfasigma, Alimentiv, BeiGene, Biora (Progenity), Celltrion, Forbion, Genentech, Gossamer Biosciences, Index Pharmaceuticals, Prometheus Biosciences, Protagonist Therapeutics, Shoreline Biosciences, Vendata Biosciences, Ventyx Biosciences, and Zealand Pharma; has stock or stock options from BeiGene, Biora (Progenity), Gossamer Bio, Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, and Vivreon Biosciences; and is an employee at Shoreline Biosciences and Ventyx Biosciences. His spouse has received consulting fees from Iveric Bio and has stock or stock options in Iveric Bio, Prometheus Biosciences, Prometheus Laboratories, Ventyx Biosciences, and Vimalan Biosciences. B.E.S. has received consultancy fees from AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celgene, Celltrion Healthcare, ClostraBio, Equillium, Enthera, Evommune, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Morphic Therapeutic, MRM Health, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma Global, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Ventyx Biosciences, and Viela Bio; has received consultancy fees, speaking fees, research grants, or other support from Abivax, Bristol Myers Squibb, Janssen, Lilly, Pfizer, Takeda, and Theravance Biopharma; has stock or stock options in Ventyx Biosciences. S.U. and R.S.M. are employees of Takeda Pharmaceuticals U.S.A., Inc. and hold stock or stock options. R.M.Q.K. is a former employee of Takeda Pharmaceuticals U.S.A., Inc. and holds stock or stock options. (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu