Abstract

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

Clin Gastroenterol Hepatol. 2023 Sep;21(10):2616-2628.e7.doi: 10.1016/j.cgh.2022.12.029. Epub 2023 Jan 6.

 

William J Sandborn 1Silvio Danese 2Jaroslaw Leszczyszyn 3Jacek Romatowski 4Engin Altintas 5Elena Peeva 6Mina Hassan-Zahraee 7Michael S Vincent 7Padmalatha S Reddy 7Christopher Banfield 7Mikhail Salganik 7Anindita Banerjee 7Jeremy D Gale 7Kenneth E Hung 7

 
     

Author information

1University of California San Diego, La Jolla, California. Electronic address: wsandborn@health.ucsd.edu.

2Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.

3Melita Medical, Gastroenterology, Wroclaw, Poland.

4Provincial Complex Hospital, Gastroenterology, Bialystok, Poland.

5Mersin University, Gastroenterology, Mersin, Turkey.

6Pfizer Global Research and Development, Cambridge, Massachusetts.

7Pfizer Inc, Early Clinical Development, Cambridge, Massachusetts.

Abstract

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 2013-2024 GI Health Foundation. All rights reserved.
This site is maintained as an educational resource for US healthcare providers only. Use of this website is governed by the GIHF terms of use and privacy statement.