Immunologic Therapies for Psoriasis

Abstracts & Commentary

Synopsis: Two injectable biologic therapies, etanercept and efalizumab, have been shown to be highly effective in treating psoriasis. Etanercept has been used in rheumatoid arthritis since 1998, and efalizumab is a new agent in phase III trials. Psoriasis is a debilitating autoimmune illness, and these new therapies, while expensive, will be a welcome addition for patients suffering from a severe form of this disease.

Sources: Lebwohl M, et al. N Engl J Med. 2003;349:2004-2013; Leonardi CL, et al. N Engl J Med. 2003;349:2014-2022.

Chronic plaque psoriasis affects 2% of the population, and these 2 studies argue that its disability is similar to other major illnesses such as diabetes, arthritis, depression, and cancer. Current therapies are limited by their toxicity and have low efficacy. Psoriasis is an incurable autoimmune disease that is mediated by T lymphocytes. The unique immunologic features of the skin, which protect it from infection, may be manipulated in treating psoriasis.

In the study by Lebwohl and associates using the T-cell modulator, efalizumab, 597 patients received weekly injections of 1 or 2 mg/kg of body weight of drug or placebo for 12 weeks. The response rate of at least 75% improvement was 22% of patients receiving 1 mg and 28% receiving 2 mg, compared with 5% receiving placebo. The responders were continued in therapy for 24 weeks with continued improvement that lasted in 30% of patients 12 weeks after discontinuation of therapy. Pictures of study patients in the article show the dramatic results, which became apparent in responders as soon as 4 weeks of therapy. Adverse side effects of the drug were mild, with headache being the most common. Efalizumab is made by Genetech, which funded the study.

In the study by Leonardi and colleagues, using etanercept, 672 patients were randomized to 3 dosages of the drug and placebo. Etanercept is a tissue necrosis factor (TNF) antagonist. TNF is involved in T-cell signaling, and its inhibition is helpful in a wide variety of inflammatory, autoimmune diseases. The response rate of at least 75% improvement over 12 weeks was achieved by just 14% of patients receiving 25 mg once weekly, but 34% of patients receiving 25 mg twice weekly, and 49% of patients receiving 50 mg twice weekly. The placebo response rate was 4% of patients. Ninety percent of patients receiving the medium- and high-dose therapy had at least a 50% improvement in lesions. The drug responders showed continued improvement for the 24-week treatment period. Adverse events and infections were mild.

Comment by Joseph E. Scherger, MD, MPH

The results of these studies are impressive and most likely represent a breakthrough in the treatment of psoriasis. It is unfortunate that less than 50% of patients have the 75% improvement of their disease. This therapy is expensive and should be reserved mainly for patients disabled by their disease, or have widespread lesions. In an accompanying editorial, Kupper further describes the immunologic targets in psoriasis, and predicts that biologic therapies for this disease and others will increase in number.1 He also states that genetic testing is likely to predict which patients will respond to biologic therapies. 

Reference

1. Kupper TS. N Engl J Med. 2003;349:1987-1990.

Dr. Scherger is Clinical Professor, University of California, San Diego.