Ritlecitinib, brepocitinib superior to placebo for inducing remission in UC

Ritlecitinib and brepocitinib as induction therapies for ulcerative colitis (UC) appear to be more effective than placebo while having an acceptable short-term safety profile, according to the results of a phase IIb study.

The study parallel-arm, double-blind umbrella study included 319 patients with active, moderate-to-severe UC. They were randomly assigned to groups receiving 8-week induction therapy with ritlecitinib (20, 70, 200 mg), brepocitinib (10, 30, 60 mg), or placebo once daily.

A total of 317 patients received treatment, with 150 on ritlecitinib, 142 on brepocitinib, and 25 on placebo. The primary endpoint of total Mayo Score (TMS) at week 8 was significantly lower with ritlecitinib and brepocitinib. The placebo-adjusted mean TMSs were −2.0 (95 percent confidence interval [CI], −3.2 to −0.9), −3.9 (95 percent CI, −5.0 to −2.7), and −4.6 (95 percent CI, −5.8 to −3.5) with ritlecitinib 20, 70, and 200 mg (p=0.003, p<0.001, p<0.001), respectively; and −1.8 (95 percent CI, −2.9 to −0.7), −2.3 (95 percent CI, −3.4 to −1.1), and −3.2 (95 percent CI, −4.3 to −2.1) for brepocitinib 10, 30, and 60 mg (p=0.009, p=0.001, p<0.001), respectively.

The placebo-adjusted proportions of patients with modified clinical remission at week 8 were 13.7 percent, 32.7 percent, and 36.0 percent with ritlecitinib 20, 70, and 200 mg, respectively; and 14.6 percent, 25.5 percent, and 25.5 percent with brepocitinib 10, 30, and 60 mg, respectively.

Most adverse events were mild, and none of the patients developed serious cases of herpes zoster infection. Infections were reported in 16.9 percent of patients on brepocitinib, 8.7 percent on ritlecitinib, and 4.0 percent on placebo. One patient on ritlecitinib died due to myocardial infarction, and another patient on brepocitinib experienced a thromboembolic event; both events were considered unrelated to the drugs.