A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha 4 integrin in active Crohn's disease

Background & Aims: alpha4 integrins are important mediators of leukocyte mi gration across vascular endothelium. This pilot placebo-controlled study ai med to assess the safety and efficacy of natalizumab, a recombinant humaniz ed monoclonal antibody to alpha4 integrin, in patients with mild to moderat ely active Crohn's disease. Methods: Thirty patients with active Crohn's di sease (Crohn's Disease Activity Index [CDAI] greater than or equal to 151 a nd less than or equal to 450) received a 3-mg/kg infusion of natalizumab (n = 18) or placebo (n = 12) by double-blind randomization. The study's prima ry endpoint was change in CDAI at week 2. Results: At week 2, the CDAI decr eased significantly from baseline after infusion of natalizumab (mean 45 po ints) but hot placebo (mean 11 points). Seven (39%) natalizumab-treated pat ients achieved remission at week 2, compared with 1 (8%) treated with place bo. In contrast, 4 (33%) of the placebo-treated patients required rescue me dication by week 2, compared with 2 (11%) natalizumab-treated patients. Sig nificant increases In circulating B and T lymphocytes were detected only af ter natalizumab administration. The frequency of commonly reported adverse events did not differ significantly between groups. Conclusions: A single 3 -mg/kg natalizumab infusion was well tolerated by Crohn's disease patients, although the dose used may have been suboptimal. Elevated circulating lymp hocyte levels after natalizumab suggest interrupted lymphocyte trafficking. Natalizumab therapy in active Crohn's disease merits further investigation .