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The Biologic Age Is Upon Us -- In Full Swing!

The biologic agents efalizumab and etanercept show promise as psoriasis therapy in two new studies.

A new wave in psoriasis therapy began with the observation that cyclosporine was an effective treatment. This observation led to the development of compounds that target the immunologic and inflammatory cascades, including agents that interrupt T-cell interactions, such as alefacept and efalizumab, and anti-tumor necrosis factor therapies, like etanercept, adalimumab, and infliximab. Two recent, placebo-controlled reports documenting the effectiveness of the biologic agents etanercept and efalizumab are the culmination of a large body of work and likely represent the first of many publications about these agents.

Lebwohl and colleagues report a phase III, multicenter, randomized, double-blind study of efalizumab at a dosage of 1 mg/kg or 2 mg/kg per week for 12 weeks. Some patients who reached the primary endpoint of 75% improvement in the PASI score were randomized a second time to receive placebo, continued therapy, or dose escalation. At least 75% improvement occurred in 22% of efalizumab recipients and was generally sustained during therapy. Patients given more than 1 mg/kg/week did not fare better than those receiving lower dosages. Adverse events were similar in the placebo and efalizumab groups, except that headache, fever, chills, nausea, and myalgias occurred more often in the treatment groups, for the most part, early in treatment. Nine percent of efalizumab recipients rebounded, but most relapses occurred as therapy ceased, and the authors suggest that tapering might reduce this occurrence.

Leonardi and colleagues conducted a multicenter, randomized, double-blind study of etanercept that also involved multiple dosing regimens, including placebo, 25 mg once per week, 25 mg twice weekly, and 50 mg twice weekly. At the 12-week endpoint, 75% PASI score improvement occurred in 14%, 34%, and 49% of patients taking etanercept, respectively, and in 4% of controls. Response continued to improve during therapy, reaching 25%, 44%, and 59% for the 486 patients receiving low, medium, and high doses at 24 weeks. There were no significant differences in toxicity between placebo and etanercept recipients. Antibodies directed against efalizumab occurred in 5% of patients in the first study, and anti-etanercept antibodies occurred in 8 patients in the second study, but the presence of antibodies did not affect efficacy.

Comment: Comparisons among biologic agents are inevitable. In these studies, etanercept appeared to produce a better response than efalizumab did, and responses improved with increased doses of etanercept but not of efalizumab. Although these agents appear to be safe, long-term use may result in toxicity, and careful monitoring programs are now being implemented. Efalizumab recently gained FDA approval, and these data suggest that FDA approval of etanercept for psoriasis therapy is not far off.

— Jeffrey P. Callen, MD

Published in Journal Watch Dermatology November 26, 2003

Citation(s):

Lebwohl M et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 2003 Nov 20; 349:2004-13.

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Leonardi CL et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003 Nov 20; 349:2014-22.

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Kupper TS. Immunologic targets in psoriasis. N Engl J Med 2003 Nov 20; 349:1987-90.

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• Medline abstract (Free)