Intest Res.  2019 Jul;17(3):375-386. 10.5217/ir.2018.00141.

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

• Hibi T
• Motoya S
• Ashida T
• Sai S
• Sameshima
• Nakamura S
• Maemoto A
• Nii M
• Sullivan B
• Gasser Jr
• Suzuki Y

• KMID: 2454746
• DOI: http://doi.org/10.5217/ir.2018.00141

Abstract

BACKGROUND/AIMS
Inhibition of α4β7 integrin 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 α4β7 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.

Keyword

Colitis, ulcerative; Japan; AMG 181; Abrilumab

MeSH Terms

Asian Continental Ancestry Group*
Colitis, Ulcerative*
Follow-Up Studies
Humans
Japan
Leukoencephalopathy, Progressive Multifocal
Ulcer*

Figure

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  Fig. 1. Study design. aScreening could be performed up to 3 times; patients who did not complete the initial screening or did not meet the eligibility criteria at the initial screening were permitted to be screened again up to 2 times; bFor patients who discontinued the study drug, the 28-week safety follow-up and the 104-week progressive multifocal leukoencephalopathy (PML) follow-up were carried out after the last dose of the study drug. E, enrolment; R, randomization.

• 

  Fig. 2. Patient disposition. aThe 3 patients who discontinued the double-blind (DB) period all completed the safety follow-up (SF) period. OL, open-label; AE, adverse event.

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