Psoriasis as a Model for T-Cell–Mediated Disease: Immunobiologic and Clinical Effects of Treatment With Multiple Doses of Efalizumab, an Anti–CD11a Antibody

BACKGROUND Leukocyte function–associated antigen 1 (LFA-1), consisting of CD11a and CD18 subunits, plays an important role in T-cell activation and leukocyte extravasation. OBJECTIVE To test whether blocking CD11a decreases immunobiologic and clinical activity in psoriatic plaques. DESIGN Open-label, multicenter, dose escalation study. PATIENTS Thirty-nine patients with moderate-to-severe psoriasis. INTERVENTION Intravenous infusions of efalizumab, a humanized anti-CD11a monoclonal antibody, for 7 weeks at doses of 0.1 mg/kg every other week or 0.1 mg/kg weekly (category 1), 0.3 mg/kg weekly (category 2), and 0.3 increasing to 0.6 or 1.0 mg/kg weekly (category 3). Skin biopsies were performed on days 0, 28, and 56. MAIN OUTCOME MEASURES Serum efalizumab levels, levels of total and unoccupied T-cell CD11a, T cell counts, epidermal thickness, cutaneous intercellular adhesion molecule 1 (ICAM-1) and keratin 16 (K16) expression, Psoriasis Area and Severity Index (PASI) scores. RESULTS Dose-response relationships were observed for pharmacokinetics and pharmacodynamic measures. Category 1 failed to maintain detectable serum efalizumab or T cell CD11a down-modulation between doses. Category 2 achieved both. Category 3 achieved both and additionally maintained sustained T-cell CD11a saturation between doses. A dose-response relationship was also observed clinically and histologically. The mean decrease in the PASI score was 47% in category 3, 45% in category 2, and 10% in category 1 (P