Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin.

Abstract

BACKGROUND & AIMS:

Selective blockade of lymphocyte-vascular endothelium interactions in the gastrointestinal tract is a promising therapeutic strategy for inflammatory bowel disease. This randomized, double-blind, controlled trial assessed the efficacy and safety of MLN0002, a monoclonal antibody targeting the alpha4beta7 integrin, in patients with active Crohn's disease.

METHODS:

Patients were randomized to receive MLN0002 2.0 mg/kg (n = 65), MLN0002 0.5 mg/kg (n = 62), or placebo (n = 58) by intravenous infusion on days 1 and 29. The primary efficacy end point was clinical response (>or=70-point decrement in the Crohn's Disease Activity Index [CDAI] score) on day 57. Secondary end points were the proportions of patients with clinical remission (CDAI score <or=150) and with an enhanced clinical response (>or=100-point decrement in CDAI). Human anti-human antibody levels were measured.

RESULTS:

Clinical response rates at day 57 were 53%, 49%, and 41% in the MLN0002 2.0 mg/kg, MLN0002 0.5 mg/kg, and placebo groups. Clinical remission rates at day 57 were 37%, 30%, and 21%, respectively (P = .04 for the 2.0 mg/kg vs placebo comparison). At day 57, 12% and 34% of patients in the 2.0- and 0.5-mg/kg groups had clinically significant human anti-human antibody levels (titers > 1:125). There was one infusion-related hypersensitivity reaction. The most common serious adverse event was worsening of Crohn's disease.

CONCLUSIONS:

This phase 2 study was suggestive of a dose-dependent beneficial effect of MLN0002 therapy on clinical remission. MLN0002 was well tolerated in patients with active Crohn's disease.

• Authors: Brian G Feagan, Gordon R Greenberg, Gary Wild, Richard N Fedorak, Pierre Paré, John W D McDonald, Albert Cohen, Alain Bitton, Jeffrey Baker, Réjean Dubé, Steven B Landau, Margaret K Vandervoort, Asit Parikh
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 6 Issue 12 Pg. 1370-7 (Dec 2008) ISSN: 1542-7714 [Electronic] United States
• PMID: 18829392 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Integrins
• Placebos
• integrin alpha4beta7
• vedolizumab

Topics

• Adult
• Anti-Inflammatory Agents (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Crohn Disease (drug therapy)
• Double-Blind Method
• Female
• Humans
• Infusions, Intravenous
• Integrins (antagonists & inhibitors)
• Male
• Middle Aged
• Placebos (administration & dosage)
• Severity of Illness Index
• Treatment Outcome