Subcutaneously administered efalizumab (anti-CD11a) improves signs and symptoms of moderate to severe plaque psoriasis

Background: Phase I and Phase II studies in patients with moderate to severe plaque psoriasis demonstrated that intravenous (IV) efalizumab improved clinical signs and symptoms and was well tolerated. Objective: To determine if subcutaneous (SC) delivery of efalizumab improves chronic plaque psoriasis and demonstrates an acceptable safety profile. Methods: This was a Phase I, open-label, single- and multiple-dose, escalating-dose study. Subjects received a single dose of efalizumab (0.3 mg/kg/wk SC) or escalating multiple doses of efalizumab (0.50-2.0 mg/kg/wk SC). Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI), target lesion assessment, and Physician's Global Assessment (PGA). Safety was assessed by evaluating adverse events, clinical laboratory test results, physical examination results, immunologic responses, and vital signs. Results: PASI score, target lesion assessment, and PGA showed improvement of approximately 40%-60% in signs and symptoms of plaque psoriasis by day 56. Mean PASI scores were still declining at the end of the eight-week dosing period, suggesting that longer duration of treatment would be more effective. By day 91, mean PAST scores were 16.2 vs. 14.6 at day 56 in the 0.5-1.0-mg/kg/wk group and 11.7 vs. 10.1 in the 1.0-2.0-mg/kg/wk group. This demonstrates that, on average, patients maintained their treatment benefit during the 42-day followup period. Overall, there were considerably fewer adverse events than in previous W studies. These consisted principally of mild to moderate headache, pain, and rhinitis. No allergic reactions were observed. Antibodies to efalizumab were observed in only one subject (2%) and did not have any clinical relevance. Conclusion: The SC administration of eight weekly doses of efalizumab improves signs and symptoms of psoriasis. The treatment was safe and very well tolerated. In comparison to previously published results with IV efalizumab, SC administration of efalizumab improves overall safety and tolerability, with the additional advantage of greater convenience.