Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis

Background: CD11a/CD18 comprise subunits of leukocyte function associated a ntigen (LFA-1), a T-cell surface molecule important in T-cell activation, T -cell emigration into skin, and cytotoxic T-cell function. Objective: We explored the immunobiologic and clinical effects of treating moderate to severe psoriasis vulgaris with a single dose of humanized monoc lonal antibody against CD11a (hu1124). Methods: This was an open label study with a single dose of hu1124 at doses of 0.03 to 10 mg/kg. Clinical (Psoriasis Area and Severity Index [PASI]) a nd immunohistologic parameters (epidermal thickness, epidermal and dermal T -cell numbers, and keratinocyte intercellular adhesion molecule 1 [ICAM-1] expression) were followed. Results: Treatment with hu1124, at doses higher than 1.0 mg/kg (group III), completely blocks CD11a staining for at least 14 days in both blood and ps oriatic plaques. At 0.3 to 1.0 mg/kg, T-cell CD11a staining was completely blocked; however, blockade lasted less than 2 weeks (group II). Only partia l saturation of either blood or plaque cellular CD11a was observed at doses of hu1124 between 0.01 and 0.1 mg/kg (group I). This pharmacodynamic respo nse was accompanied by decreased numbers of epidermal and dermal CD3(+) T c ells, decreased keratinocyte and blood vessel expression of ICAM-1, and epi dermal thinning. Statistically significant drops in PASI compared with base line were observed in group II patients at weeks 3 and 4 and in group III p atients at weeks 2 through 10. No significant drop in PASI score was observ ed in group 1. Adverse events were mild at doses of 0.3 mg/kg or less and i ncluded mild chills, abdominal discomfort, headache, and fever. At a single dose of 0.6 mg/kg or higher, headache was the most common dose-limiting to xicity observed. Conclusion: Targeting CD11a may improve psoriasis by inhibiting T-cell acti vation, T-cell emigration into the skin, and cytotoxic T-cell function.