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Arch Dermatol. 2002 May;138(5):591-600.

Psoriasis as a model for T-cell-mediated disease: immunobiologic and clinical effects of treatment with multiple doses of efalizumab, an anti-CD11a antibody.

Author information

1
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Clinical Research Center, New Brunswick, NJ 08903-0019, USA. gottliab@UMDNJ.EDU

Abstract

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<.001). Epidermal and dermal T-cell counts, epidermal thickness, and ICAM-1 and K16 expression decreased in categories 2 and 3 but not in category 1. Circulating lymphocyte counts increased in categories 2 and 3.

CONCLUSIONS:

At doses of 0.3 mg/kg or more per week, intravenous efalizumab produced significant clinical and histologic improvement in psoriasis, which correlated with sustained serum efalizumab levels and T-cell CD11a saturation and down-modulation.

PMID:
12020219
DOI:
10.1001/archderm.138.5.591
[Indexed for MEDLINE]

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