Advances in psoriasis

Psoriasis is a chronic skin disorder that affects approximately 2 percent of the U.S. and European population.

Over the last several years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies.

Jeffrey M. Weinberg, M.D., assistant clinical professor of dermatology, Columbia University, reviewed the progress of four biologic agents in a seminar yesterday which are available or are under investigation for clinical use: infliximab, etanercept, efalizumab and alefacept.

In the first 10 weeks of a phase 2 trial evaluating infliximab, the percentage of patients reaching PASI 75 at week 10 were: 6 percent for placebo, 72 percent for 3 mg/kg infliximab, and 88 percent for 5 mg/kg infliximab.

In a phase 3 study evaluating etanercept, the drug was evaluated at doses of 25 mg and 50 mg subcutaneously twice weekly. At the 25 mg dose, the percentage of patients achieving PASI 75 was 34 percent at 12 weeks and 49 percent at 24 weeks. At the 50 mg dose, the percentage of patients achieving PASI 75 was 49 percent at 12 weeks and 59 percent at 24 weeks.

In two phase 3 trials with subcutaneous efalizumab, subjects were randomized to treatment consisting of an initial conditioning dose of 0.7 mg/kg in week 1, followed by 11 weekly doses of either 1.0 mg/kg or 2.0 mg/kg of efalizumab or placebo. For the 1.0 mg/kg/week group, 29.2 percent achieved PASI; for the 2.0 mg/kg/week group, 27.6 percent achieved PASI 75. For patients in the placebo group, 3.4 percent achieved PASI 75.

A phase 3 trial evaluated intramuscular (IM) alefacept 15 mg once a week for 12 weeks, IM alefacept 10 mg once a week for 12 weeks, or placebo. Two weeks after the last dose was given, 21 percent of patients treated with the 15 mg dose achieved at lease a 75 percent reduction from baseline in their PASI score compared with 5 percent of patients receiving placebo, according to Dr. Weinberg.

Another phase 3 study evaluated the efficacy and tolerability of once-weekly alefacept 7.5 mg administered by intravenous bolus in patients. This study consisted of two treatment courses, each with a 12-week treatment and a 12-week follow-up phase. During the first course of treatment, 14 percent and 4 percent of patients receiving alefacept and placebo respectively, achieved 75 percent improvement in PASI at week 14. Patients randomized to receive two courses of alefacept showed additional improvement at the end of the second course of therapy with 40 percent achieving 75 percent and 50 percent PASI improvement at any time.

All four drugs were generally well-tolerated.