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Psoriasis as a Model for T-Cell–Mediated Disease
Immunobiologic and Clinical Effects of Treatment With Multiple Doses of Efalizumab, an Anti–CD11a Antibody
Alice B. Gottlieb, MD, PhD;
James G. Krueger, MD, PhD;
Knut Wittkowski, DSc, PhD;
Russell Dedrick, PhD;
Patricia Ann Walicke, MD, PhD;
Marvin Garovoy, MD
Arch Dermatol. 2002;138:591-600.
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.
From the Clinical Research Center, University of Medicine and Dentistry
of New Jersey–Robert Wood Johnson Medical School, New Brunswick (Dr
Gottlieb); Laboratory for Investigative Dermatology, The Rockefeller University,
New York, NY (Drs Krueger and Wittkowski); XOMA (US), LLC, Berkeley, Calif
(Drs Dedrick and Garovoy), and Genentech, Inc, South San Francisco, Calif
(Dr Walicke).
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