Efficacy and Safety of Abrilumab in a Randomized, Placebo-Controlled Trial for Moderate-to-Severe Ulcerative Colitis

William J. Sandborn, Marcoli Cyrille, Mark Berner Hansen, Brian G. Feagan, Edward V. Loftus, Gerhard Rogler, Severine Vermeire, Martha L. Cruz, Jun Yang, Michael J. Boedigheimer, Lubna Abuqayyas, Christine M. Evangelista, Barbara A. Sullivan, Walter Reinisch

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background & Aims: The α 4 β 7 integrin is a validated target in inflammatory bowel disease. This randomized, phase 2b, placebo-controlled, double-blind study evaluated the efficacy and safety of the anti-α 4 β 7 antibody abrilumab in patients with moderate-to-severe ulcerative colitis despite treatment with conventional therapies. Methods: Patients (total Mayo Score 6–12, recto-sigmoidoscopy score ≥2) with inadequate response or intolerance to conventional therapies were randomized to receive subcutaneous abrilumab (7, 21, or 70 mg) on day 1, weeks 2 and 4, and every 4 weeks; abrilumab 210 mg on day 1; or placebo. The primary end point was remission (total Mayo Score ≤2 points, no individual sub-score >1 point) for the 2 highest dosages at week 8. Key secondary end points were response and mucosal healing (centrally read) at week 8. Results: For 354 patients who received ≥1 dose of investigational product (placebo, n = 116; 7 mg, n = 21; 21 mg, n = 40; 70 mg, n = 98; 210 mg, n = 79), non-adjusted remission rates at week 8 were 4.3%, 13.3%, and 12.7% for the placebo and abrilumab 70-mg and 210-mg groups, respectively (P <.05 for 70 and 210 mg vs placebo); odds of achieving remission were significantly greater with abrilumab 70 mg (odds ratio 3.35; 90% CI 1.41–7.95; P =.021) and 210 mg (odds ratio 3.33; 90% confidence interval 1.34–8.26; P =.030) than with placebo. Response and mucosal healing rates with these dosages also were significantly greater than with placebo. Higher baseline α 4 β 7 levels on naïve CD4 + T cells were a prognostic indicator for overall outcome, but not a predictive biomarker of abrilumab response. There were no cases of progressive multifocal leukoencephalopathy or deaths. Conclusions: Abrilumab treatment for 8 weeks induced remission, clinical response, and mucosal healing in patients with moderate-to-severe ulcerative colitis. ClinicalTrials.gov, number NCT01694485.

Original languageEnglish (US)
Pages (from-to)946-957.e18
JournalGastroenterology
Volume156
Issue number4
DOIs
StatePublished - Mar 2019

Keywords

  • Abrilumab
  • Ulcerative Colitis
  • α β

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Sandborn, W. J., Cyrille, M., Hansen, M. B., Feagan, B. G., Loftus, E. V., Rogler, G., Vermeire, S., Cruz, M. L., Yang, J., Boedigheimer, M. J., Abuqayyas, L., Evangelista, C. M., Sullivan, B. A., & Reinisch, W. (2019). Efficacy and Safety of Abrilumab in a Randomized, Placebo-Controlled Trial for Moderate-to-Severe Ulcerative Colitis. Gastroenterology, 156(4), 946-957.e18. https://doi.org/10.1053/j.gastro.2018.11.035