Natalizumab is a humanized IgG4 monoclonal antibody against 4 integrin that inhibits both 4 7- MadCAM-1 and 4 1-vascular cellular adhesion molecule 1 binding. Natalizumab failed to demonstrate efficacy for induction of response or remission in several Crohn's disease controlled trials (Ghosh et al. 2003; Gordon et al. 2001; Sandborn et al. 2005d). In the ENACT-1 (Efficacy of Natalizumab as Active Crohn's Therapy) study, natalizumab was shown to be efficacious for maintenance of response and remission through 36 weeks in those patients who had an initial response (Sandborn et al. 2005d). The ENACT-1 study was the largest phase 3 trial ever conducted in CD. A total of 905 patients received natalizumab (300 mg IV) or placebo at Weeks 0,4, and 8ina4:1 randomization. The primary endpoints of clinical response (CDAI reduction of > 70) and clinical remission (CDAI <150) at Week 10 were not achieved. Approximately 40% of patients in both groups had previously received infliximab. Among patients with elevated baseline CRP levels, 42 % of those treated with natalizumab achieved clinical remission versus 29 % of patients receiving placebo.
In the Evaluation of Natalizumab as Continuous Therapy (ENACT-2) trial (Sandborn et al. 2005d), patients from ENACT-1 who responded to therapy received 300 mg natalizumab every 4 weeks. Of the natalizumab group, 44% of patients achieved sustained remission as compared with 26% of the placebo group (p <0.001). Natalizumab was well tolerated in these studies. Reports of progressive multifocal leukoencephalopathy led to suspension of pursuit of this agent. However, analysis of worldwide safety data revealed no further problems, and studies in Crohn's disease are expected to resume in the near future (Vermeire and Rutgeerts 2006).
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