Natalizumab: pharmacology, clinical efficacy and safety in the treatment of patients with Crohn's disease.

Natalizumab is a humanized monoclonal antibody against alpha4 integrin. In preclinical and clinical studies, natalizumab, which interferes with leukocyte trafficking in the intestinal tract, demonstrated effectiveness in inducing clinical response and maintaining remission in patients with moderate-to-severely active Crohn's disease. However, during clinical trials, three natalizumab-treated patients (one Crohn's disease patient and two multiple sclerosis patients) developed progressive multifocal leukoencephalopathy (PML). As a consequence of this unexpected serious adverse event, a retrospective safety evaluation was conducted; in that safety evaluation, no new cases of PML were identified. Natalizumab returned to the market in June 2006 for the treatment of relapsing multiple sclerosis. As of May 2007, an estimated 12,000 patients worldwide had received natalizumab, with no new confirmed cases of PML or opportunistic infections reported. Natalizumab is currently being investigated for use in treating patients with Crohn's disease. If it is approved for treatment of Crohn's patients, the clinical benefit of natalizumab should be weighed carefully against the potential risk of serious adverse events.