SAN FRANCISCO — Efalizumab appears to be well tolerated over the course of up to 60 weeks of treatment, according to a combined analysis of more than 1,000 patients with moderate to severe chronic plaque psoriasis.
Common adverse events were similar to those seen in shorter trials; no new category of common adverse event appeared during extended therapy periods, Dr. Alice B. Gottlieb reported in a poster session at the annual meeting of the American Academy of Dermatology.
The risk of serious adverse events did not increase over time, added Dr. Gottlieb of the University of Medicine and Dentistry of New Jersey, New Brunswick, N.J. Dr. Gottlieb is a paid consultant for Genentech Inc., which makes efalizumab (Raptiva). The Food and Drug Administration approved the biologic agent for the treatment of moderate to severe psoriasis in October 2003.
The analysis appears to be the largest compilation of psoriasis patients studied through 60 weeks of treatment with a biologic therapy.
Dr. Gottlieb and her associates evaluated the long-term safety of efalizumab, injected subcutaneously at weekly intervals, by pooling the 60-week data from two multicenter phase III studies of adults with moderate to severe chronic plaque psoriasis. The Psoriasis Area and Severity Index (PASI) of the patients was at least 12 at baseline; their mean PASI was 19. At least 10% of their body surface area was affected; the mean was 29%.
One study was a 60-week randomized, double-blind, parallel-group, placebo-controlled trial. Included in the pooled analysis were 450 patients who had been randomized to receive efalizumab during the 12-week placebo-controlled portion of the trial and 218 who were randomized to receive placebo. Both groups entered an open-label extended-treatment phase for up to 48 weeks of active treatment, and then were eligible to continue to receive the drug for another 12 weeks or until the drug became commercially available.
The second study included in the pooled analysis was an open-label 36-month trial. The investigators evaluated safety data for up to 60 weeks of therapy for 339 of the patients.
Concomitant use of topical psoriasis therapy or phototherapy was permitted at various periods in both studies. For analysis, the investigators divided treatment phases into five consecutive 12-week segments. During the first 12-week exposure period, 80% of 1,004 patients experienced at least one adverse event. These occurred most often within 48 hours of efalizumab injection, and consisted primarily of headache, fever, chills, nausea, pharyngitis, and a flulike syndrome. The percentage of patients experiencing an adverse event then gradually decreased to 48% among the 537 patients followed for 49–60 weeks, Dr. Gottlieb wrote.
Infections occurred in 20%–30% of patients during each of the five evaluation periods. Arthritis occurred in 1%–3% of patients throughout the five periods.
Serious adverse events were noted in 2%–3% of patients during each 12-week segment. The incidence of each serious event was less than 1%, except for serious skin-related problems, which peaked at 1% during the 37–48 week exposure period. There was one case of hemolytic anemia that occurred with 25–36 weeks of exposure. Eight cases of thrombocytopenia were reported; two occurred during the first 12 weeks of exposure, three with 13–24 weeks, two with 25–36 weeks, and one with 37–48 weeks of exposure.
The incidence of malignancy remained at less than 1% throughout. The most common malignancy was nonmelanoma skin cancer, of which there were 18 cases, Dr. Gottlieb reported.