Efficacy and safety of abrilumab, an α4β7 integrin inhibitor, in Japanese patients with moderate-to-severe ulcerative colitis: a phase II study

Background/Aims: Inhibition of alpha 4 beta 7 integral has been shown to be effective for induction and maintenance therapy in patients with ulcerative colitis (UC). We investigated the effects of varying doses of the alpha 4 beta 7 inhibitor abrilumab in Japanese patients with moderate-to-severe UC despite conventional treatments. Methods: In this randomized, double-blind, placebo-controlled study, 45 UC patients were randomized to abrilumab 21 mg (n=11), 70 mg (n=12), 210 mg (n=9), or placebo (n=13) via subcutaneous (SC) injection for 12 weeks. The double-blind period was followed by a 36-week open-label period, in which all patients received abrilumab 210 mg SC every 12 weeks, and a 28-week safety follow-up period. The primary efficacy variable was clinical remission at week 8 (total Mayo score <= 2 points with no individual subscore >1 point). Results: Clinical remission at week 8 was 4 out of 31 (12.9%) overall in the abrilumab groups versus 0 out of 13 in the placebo group (abrilumab 21 mg, 1/10 [10.0%]; 70 mg, 2/12 [16.7%]; 210 mg, 1/9 [11.1%]). In both the double-blind and open-label periods, fewer patients in the abrilumab groups experienced >= 1 adverse event compared with those in the placebo group. There were no cases of progressive multifocal leukoencephalopathy and no deaths. Conclusions: Abrilumab 70 mg and 210 mg yielded numerically better results in terms of clinical remission rate at Week 8 than placebo, with the 210 mg dose showing more consistent treatment effects. Abrilumab was well tolerated in Japanese patients with UC.