OP035 Efficacy and safety of abrilumab (AMG 181/MEDI 7183) therapy for moderate to severe Crohn's disease
Sandborn W.J.1, Cyrille M.2, Berner Hansen M.3, Feagan B.G.4, Loftus Jr. E.V.5, Vermeire S.6, Cruz M.L.2, Mo M.2, Sullivan B.A.2, Reinisch W.*7
1University of California San Diego, La Jolla, United States 2Amgen Inc., Thousand Oaks, United States 3University of Copenhagen, Copenhagen, Denmark 4Robarts Research Institute, University of Western Ontario, London, Canada 5Mayo Clinic, Division of Gastroenterology and Hepatology, Rochester, United States 6University Hospitals Leuven, Leuven, Belgium 7Medical University Vienna, Vienna, Austria
Adhesion molecule α4β7 is a validated treatment target in inflammatory bowel diseases. We evaluated abrilumab, a fully human monoclonal antibody against α4β7, in patients with moderate to severe Crohn's disease (CD).
This phase 2b, randomised, multi-centre, double-blind, placebo (Pbo)-controlled study enrolled patients aged 18–65 years with moderate to severe CD (CDAI score 220–450) and evidence of active inflammation (by endoscopic evaluation, or elevated C-reactive protein or fecal calprotectin). In addition, patients must have had inadequate or loss of response or intolerance to immunosuppressives, TNF antagonists, or corticosteroids. Eligible patients were randomised to receive Pbo or abrilumab (21 or 70 mg) SC on day 1, weeks 2 and 4, and every 4 weeks (Q4W) for up to 24 weeks, or one dose of abrilumab 210 mg SC on day 1. The primary endpoint was CDAI remission (score <150) at week 8. Key secondary endpoints were remission at week 12 and CDAI response (reduction from baseline of ≥100) at weeks 8 and 12. CD4+ T cell subsets were enumerated and α4β7 receptor occupancy was measured in a subgroup of patients.
This study enrolled 249 patients. Final randomisation allocation was affected by a systematic misalignment in investigational product, resulting in 98, 26, 84, and 41 patients in the Pbo, 21 mg Q4W, 70 mg Q4W, and 210 mg treatment groups, respectively. The study blind and randomisation were intact. Baseline demographics were similar. Statistically significant improvement was not achieved between the abrilumab 70 mg Q4W and Pbo arms for the primary endpoint (
Although the primary endpoint was not met, beneficial effects of abrilumab were observed for remission and response rates. There was no safety imbalance compared with Pbo.
Amgen and AstraZeneca/MedImmune sponsored this study.