Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin
- PMID:18829392
- DOI: 10.1016/j.cgh.2008.06.007
Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin
Erratum in
- Clin Gastroenterol Hepatol. 2009 Apr;7(4):494
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.
Trial registration: ClinicalTrials.govNCT00655135.
Comment in
- Veto on vedolizumab (MLN0002) for Crohn's disease.Baumgart DC.Baumgart DC.Inflamm Bowel Dis. 2010 Mar;16(3):537-8. doi: 10.1002/ibd.21078.Inflamm Bowel Dis. 2010.PMID:19685452No abstract available.
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