Treatment of Psoriasis with Alefacept: Correlation of Clinical Improvement with Reductions of Memory T-Cell Counts

Kenneth B. Gordon*, Akshay K. Vaishnaw, John O'Gorman, Jeff Haney, Alan Menter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1563-1570
Number of pages8
JournalArchives of dermatology
Volume139
Issue number12
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Dermatology

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