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Correlation of Clinical Improvement With Reductions of Memory T-Cell Counts

Kenneth B. Gordon, MD; Akshay K. Vaishnaw, MD; John O'Gorman, PhD; Jeff Haney, MA; Alan Menter, MD; for the Alefacept Clinical Study Group

Arch Dermatol. 2003;139:1563-1570.

Objective  To examine the relationship between the pharmacodynamic and antipsoriatic effects of alefacept, a biologic agent that targets CD4⁺ and CD8⁺ memory T cells.

Design  Randomized, double-blind, placebo-controlled study of 3 parallel groups.

Setting  Fifty-one study centers.

Patients  Five hundred fifty-three patients with chronic plaque psoriasis.

Interventions  Patients were randomized (1:1:1) to 1 of the following 3 cohorts: alefacept, 7.5 mg, in both courses (cohort 1); alefacept, 7.5 mg, in the first course and placebo in the second course (cohort 2); or placebo in the first course and alefacept, 7.5 mg, in the second course (cohort 3). In each course, alefacept or placebo was administered by intravenous bolus once weekly for 12 weeks, followed by 12 weeks of observation.

Main Outcome Measures  Circulating lymphocyte levels and the Psoriasis Area Severity Index.

Results  One or 2 courses of alefacept reduced CD4⁺ and CD8⁺ memory T-cell counts, while sparing the naive population. At 12 weeks after the last dose of alefacept in courses 1 and 2, 88% and 83% of patients, respectively, had CD4⁺ cell counts greater than the lower limit of normal. In course 1, alefacept-treated patients with the largest decreases in memory T-cell counts experienced the greatest reductions in disease activity (P<.001). The duration of clinical benefit seemed to be longer among patients who had the greatest reduction in CD4⁺ and CD8⁺ memory T-cell counts.

Conclusions  One or 2 courses of intravenous alefacept reduced circulating memory T-cell counts while sparing the naïve T-cell population. The reductions in memory T-cell counts were related to all measures of disease activity evaluated and the duration of response to therapy, suggesting that prolonged remissions of psoriasis can be attained with reduction of the pathogenic T-cell count.

From the Department of Medicine, Division of Dermatology, Loyola University Medical Center, Maywood, Ill (Dr Gordon); Biogen, Inc, Cambridge, Mass (Drs Vaishnaw and O'Gorman); Coley Pharmaceutical Group, Inc, Wellesley, Mass (Mr Haney); and Department of Dermatology, Baylor University Medical Center, Dallas, Tex (Dr Menter). Members of the Alefacept Clinical Study Group are listed on page 1569. Drs Gordon and Menter have received research support from Biogen, Inc.

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