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Treatment of Active Crohn's Disease With MLN0002, a Humanized Antibody to the α4β7 Integrin

Published:October 02, 2008DOI:https://doi.org/10.1016/j.cgh.2008.06.007

      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 α4β7 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 (≥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 ≤150) and with an enhanced clinical response (≥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.

      Abbreviations used in this paper:

      AE (adverse event), CDAI (Crohn's Disease Activity Index), HAHA (human anti-human antibodies), IBD (inflammatory bowel disease), IBDQ (Inflammatory Bowel Disease Questionnaire), PML (progressive multifocal leukoencephalopathy), SAE (serious adverse events)
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