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

Alice Gottlieb, James G. Krueger, Ross Bright, Mark Ling, Mark Lebwohl, Sewon Kang, Steve Feldman, Mary Spellman, Knut Wittkowski, Hans D. Ochs, Paula Jardieu, Robert Bauer, Mark White, Russell Dedrick, Marvin Garovoy

Research output: Contribution to journalArticlepeer-review

Abstract

Background: CD11a/CD18 comprise subunits of leukocyte function associated antigen (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 monoclonal 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]) and immunohistologic parameters (epidermal thickness, epidermal and dermal T-cell numbers, and keratinocyte intercellular adhesion molecule I [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 psoriatic 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 partial 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 response was accompanied by decreased numbers of epidermal and dermal CD3+ T cells, decreased keratinocyte and blood vessel expression of ICAM-1, and epidermal thinning. Statistically significant drops in PASI compared with baseline were observed in group II patients at weeks 3 and 4 and in group III patients at weeks 2 through 10. No significant drop in PASI score was observed in group 1. Adverse events were mild at doses of 0.3 mg/kg or less and included 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 toxicity observed. Conclusion: Targeting CD11a may improve psoriasis by inhibiting T- cell activation, T-cell emigration into the skin, and cytotoxic T-cell function.

Original languageEnglish (US)
Pages (from-to)428-435
Number of pages8
JournalJournal of the American Academy of Dermatology
Volume42
Issue number3
DOIs
StatePublished - Mar 2000
Externally publishedYes

ASJC Scopus subject areas

  • Dermatology

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