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Previous Volume 352:2499-2507 June 16, 2005 Number 24 Next

Treatment of Ulcerative Colitis with a Humanized Antibody to the ₄₇ Integrin

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ABSTRACT

Background Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases.

Methods We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the ₄₇ integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization.

Results Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as compared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1:125 developed, incomplete saturation of the ₄₇ receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable.

Conclusions In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.

Source Information

From the Robarts Clinical Trials, Robarts Research Institute, London, Ont. (B.G.F., M.K.V.); the Departments of Medicine (B.G.F., J.W.D.M.) and Epidemiology and Biostatistics (B.G.F.), University of Western Ontario, London; the Department of Medicine, University of Toronto, Toronto (G.R.G, A.H.S.); the Department of Medicine, McGill University, Montreal (G.W., A.C.); the Department of Medicine, University of Alberta, Edmonton (R.N.F.); and the Department of Medicine, Laval University, Quebec, Que. (P.P., R.D.) — all in Canada; Dynogen Pharmaceuticals, Waltham, Mass. (S.L.); and Millennium Pharmaceuticals, Cambridge, Mass. (R.A.A., I.H.F.).

Address reprint requests to Dr. Feagan at Robarts Clinical Trials, Robarts Research Institute, 100 Perth Dr., London, ON N6A 5K8, Canada, or at bfeagan{at}robarts.ca.

Full Text of this Article

Related Letters:

Antibody to ₄₇ Integrin for Ulcerative Colitis
Danese S., De La Rue S. A., Gasbarrini A., Feagan B. G., Fox I. H., Kishimoto K.
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N Engl J Med 2005; 353:1180-1181, Sep 15, 2005. Correspondence

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