Oral Ritlecitinib and Brepocitinib for Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2b Study
口服Ritlecitinib及Brepocitinib治疗中重度溃疡性结肠炎：一项随机2b期临床研究结果
10.1016/j.cgh.2022.12.029
01-06, Article
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Background & aims:: The efficacy and safety of ritlecitinib (oral JAK3/TEC inhibitor) and brepocitinib (oral TYK2/JAK1 inhibitor) as induction therapy were assessed in patients with active, moderate-to-severe ulcerative colitis (UC).
Methods:: This phase 2b, parallel-arm, double-blind umbrella study randomized patients with moderate-to-severe UC 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% CI) at week 8 were -2.0 (-3.2, -0.9), -3.9 (-5.0, -2.7), and -4.6 (-5.8, -3.5) for ritlecitinib 20, 70, and 200 mg (P=0.003, P<0.001, P<0.001), and -1.8 (-2.9, -0.7), -2.3 (-3.4, -1.1), and -3.2 (-4.3, -2.1) for brepocitinib 10, 30, and 60 mg (P=0.009, P=0.001, P<0.001), respectively. Estimates (90% CI) 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 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 considered unrelated to study drug.
Conclusions: : Ritlecitinib and brepocitinib induction therapies were more effective than placebo for the treatment of moderate to severe active UC, with an acceptable short-term safety profile.
First Authors:
William J Sandborn
Correspondence Authors:
William J Sandborn
All Authors:
William J Sandborn,Silvio Danese,Jaroslaw Leszczyszyn,Jacek Romatowski,Engin Altintas,Elena Peeva,Mina Hassan-Zahraee,Michael S Vincent,Padmalatha S Reddy,Christopher Banfield,Mikhail Salganik,Anindita Banerjee,Jeremy D Gale,Kenneth E Hung
