Oral Ritlecitinib and Brepocitinib for Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2b Study.

Autor:	Sandborn WJ; University of California San Diego, La Jolla, California. Electronic address: wsandborn@health.ucsd.edu., Danese S; Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy., Leszczyszyn J; Melita Medical, Gastroenterology, Wroclaw, Poland., Romatowski J; Provincial Complex Hospital, Gastroenterology, Bialystok, Poland., Altintas E; Mersin University, Gastroenterology, Mersin, Turkey., Peeva E; Pfizer Global Research and Development, Cambridge, Massachusetts., Hassan-Zahraee M; Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts., Vincent MS; Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts., Reddy PS; Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts., Banfield C; Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts., Salganik M; Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts., Banerjee A; Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts., Gale JD; Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts., Hung KE; Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts.
Jazyk:	angličtina
Zdroj:	Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association [Clin Gastroenterol Hepatol] 2023 Sep; Vol. 21 (10), pp. 2616-2628.e7. Date of Electronic Publication: 2023 Jan 06.
DOI:	10.1016/j.cgh.2022.12.029
Abstrakt:	Background & Aims: The efficacy and safety of ritlecitinib (oral JAK3/TEC family kinase inhibitor) and brepocitinib (oral TYK2/JAK1 inhibitor) as induction therapy were assessed in patients with active, moderate-to-severe ulcerative colitis. Methods: This phase 2b, parallel-arm, double-blind umbrella study randomized patients with moderate-to-severe ulcerative colitis to receive 8-week induction therapy with ritlecitinib (20, 70, 200 mg), brepocitinib (10, 30, 60 mg), or placebo once daily. The primary endpoint was total Mayo Score (TMS) at week 8. Results: Of 319 randomized patients, 317 received ritlecitinib (n = 150), brepocitinib (n = 142), or placebo (n = 25). The placebo-adjusted mean TMSs (90% confidence interval) at week 8 were -2.0 (-3.2 to -0.9), -3.9 (-5.0 to -2.7), and -4.6 (-5.8 to -3.5) for ritlecitinib 20, 70, and 200 mg, respectively (P = .003, P < .001, P < .001), and -1.8 (-2.9 to -0.7), -2.3 (-3.4 to -1.1), and -3.2 (-4.3 to -2.1) for brepocitinib 10, 30, and 60 mg, respectively (P = .009, P = .001, P < .001). Estimates (90% confidence interval) for placebo-adjusted proportions of patients with modified clinical remission at week 8 were 13.7% (0.5%-24.2%), 32.7% (20.2%-45.3%), and 36.0% (23.6%-48.6%) for ritlecitinib 20, 70, and 200 mg, respectively, and 14.6% (1.9%-25.7%), 25.5% (11.0%-38.1%), and 25.5% (11.0%-38.1%) for brepocitinib 10, 30, and 60 mg, respectively. Adverse events were mostly mild, and there were no serious cases of herpes zoster infection. Infections were observed with brepocitinib (16.9% [12.5%-23.7%]), ritlecitinib (8.7% [5.2%-13.4%]), and placebo (4.0% [0.2%-17.6%]). One death due to myocardial infarction (ritlecitinib) and 1 thromboembolic event (brepocitinib) occurred; both were considered unrelated to study drug. Conclusions: Ritlecitinib and brepocitinib induction therapies were more effective than placebo for the treatment of moderate-to-severe active ulcerative colitis, with an acceptable short-term safety profile. Clinicaltrials: gov number: NCT02958865. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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