Ritlecitinib, brepocitinib outperform placebo for treatment of moderate to severe UC
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Ritlecitinib and brepocitinib induction therapies more effectively reduced total Mayo Score compared with placebo in patients with moderate to severe ulcerative colitis, according to data in Clinical Gastroenterology and Hepatology.
“The currently approved small-molecule [Janus kinase (JAK)] inhibitors for treatment of ulcerative colitis include tofacitinib, filgotinib and upadacitinib. ... The JAK inhibitor selectivity profiles may differentially impact ulcerative colitis, and the link between selective JAK inhibition and an improved benefit/risk profile has yet to be elucidated,” William J. Sandborn, MD, gastroenterologist and professor of medicine at the University of California San Diego, and colleagues wrote. “Ritlecitinib, a JAK3/tyrosine kinase expressed in hepatocellular carcinoma family inhibitor and brepocitinib, a TYK2/JAK1 inhibitor, are oral kinase inhibitors in clinical development.”
In the VIBRATO phase 2b, double-blind randomized umbrella study, Sandborn and colleagues assessed the efficacy of ritlecitinib and brepocitinib induction therapy in patients aged 18 to 75 years with moderate to severe UC.
Of 317 patients included, 150 received ritlecitinib (20 mg, n = 51; 70 mg, n = 49; 200 mg, n = 50), 142 received brepocitinib (10 mg, n = 48; 30 mg, n = 47; 60 mg, n = 47) and 25 received placebo once daily for 8 weeks. The primary endpoint was total Mayo Score (TMS) at week 8.
At the end of the study period, mean TMS was 7.9 in the placebo group and 5.9, 4 and 3.3 in the 20-mg, 70-mg and 200-mg ritlecitinib groups, respectively; In the 10-mg, 30-mg and 60-mg brepocitinib groups, mean TMSs were 6.1, 5.6 and 4.7, respectively.
Placebo-adjusted mean TMSs were –2 (90% CI, –3.2 to –0.9), –3.9 (90% CI, –5 to –2.7) and –4.6 (90% CI, –5.8 to –3.5) points for ritlecitinib groups, respectively, and –1.8 (90% CI, –2.9 to –0.7), –2.3 (90% CI, –3.4 to –1.1) and –3.2 (90% CI, –4.3 to –2.1) points for brepocitinib groups.
Further, the estimated placebo-adjusted proportions of patients with modified clinical remission were 13.7%, 32.7% and 36% for ritlecitinib groups and 14.6%, 25.5% and 25.5% for brepocitinib groups, respectively.
Treatment-emergent adverse events occurred in 46.1% of patients, including 43.3% in the ritlecitinib group, 47.9% in the brepocitinib group and 52% in the placebo group. Anemia, headache and nasopharyngitis were among the most reported all-cause adverse events.
“Induction therapies with ritlecitinib and brepocitinib were more effective than placebo for treatment of moderate to severe ulcerative colitis, with acceptable short-term safety profiles,” Sandborn and colleagues concluded.
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