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Previous Volume 349:2004-2013 November 20, 2003 Number 21 Next

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ABSTRACT

Background Interactions between leukocyte-function–associated antigen type 1 (LFA-1) and intercellular adhesion molecules are important in the pathogenesis of psoriasis. Efalizumab, a humanized monoclonal antibody, binds to the subunit (CD11a) of LFA-1 and inhibits the activation of T cells.

Methods In a phase 3, multicenter, randomized, placebo-controlled, double-blind study, we assign 597 subjects with psoriasis to receive subcutaneous efalizumab (1 or 2 mg per kilogram of body weight per week) or placebo for 12 weeks. Depending on the response after 12 weeks, subjects received an additional 12 weeks of treatment with efalizumab or placebo. Study treatments were discontinued at week 24, and subjects were followed for an additional 12 weeks.

Results At week 12, there was an improvement of 75 percent or more in the psoriasis area-and-severity index in 22 percent of the subjects who had received 1 mg of efalizumab per kilogram per week and 28 percent of those who had received 2 mg of efalizumab per kilogram per week, as compared with 5 percent of the subjects in the placebo group (P<0.001 for both comparisons). Efalizumab-treated subjects had greater improvement than those in the placebo group as early as week 4 (P<0.001). Among the efalizumab-treated subjects who had an improvement of 75 percent or more at week 12, improvement was maintained through week 24 in 77 percent of those who continued to receive efalizumab, as compared with 20 percent of those who were switched to placebo (P<0.001 for both comparisons). After the discontinuation of efalizumab at week 24, an improvement of 50 percent or more in the psoriasis area-and-severity index was maintained in approximately 30 percent of subjects during the 12 weeks of follow-up. Efalizumab was well tolerated, and adverse events were generally mild to moderate.

Conclusions Efalizumab therapy resulted in significant improvements in plaque psoriasis in subjects with moderate-to-severe disease. Extending treatment from 12 to 24 weeks resulted in both maintenance and improvement of responses.

Source Information

From the Mt. Sinai School of Medicine, New York (M.L.); the University of Texas Medical Branch, Galveston (S.K.T.); the Atlanta Dermatology, Vein, and Research Center, Alpharetta, Ga. (T.K.H.); Probity Medical Research, Windsor, Ont., Canada (D.T.); Buffalo Grove, Ill. (S.G.); the Welborn Clinic, Evansville, Ind. (N.H.T.); Genentech, South San Francisco, Calif. (P.W., W.D., X.W.); Xoma, Berkeley, Calif. (M.R.G.); and the Eastern Virginia Medical School and Virginia Clinical Research, Norfolk, Va. (D.P.).

Address reprint requests to Dr. Lebwohl at the Mt. Sinai School of Medicine, 5 E. 98th St., 12th Fl., Box 1048, New York, NY 10029-6574.

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