Treatment of psoriasis with alefacept: correlation of clinical improvement with reductions of memory T-cell counts. Arch Dermatol 2003 Dec;139(12):1563-70
Date
12/17/2003Pubmed ID
14676071DOI
10.1001/archderm.139.12.1563Scopus ID
2-s2.0-0348134794 (requires institutional sign-in at Scopus site) 90 CitationsAbstract
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.
Author List
Gordon KB, Vaishnaw AK, O'Gorman J, Haney J, Menter A, Alefacept Clinical Study GroupAuthor
Kenneth Brian Gordon MD Chair, Professor in the Dermatology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Cohort Studies
Computer Graphics
Double-Blind Method
Female
Humans
Lymphocyte Count
Male
Middle Aged
Psoriasis
Recombinant Fusion Proteins
Treatment Outcome
