Treatment of psoriasis with alefacept: correlation of clinical improvement with reductions of memory T-cell counts.
OBJECTIVE
To examine the relationship between the pharmacodynamic and antipsoriatic effects of alefacept, a biologic agent that targets CD4+ and CD8+ memory T cells.


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


METHODS
Fifty-one study centers.


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


METHODS
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.


METHODS
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.
Gordon
Kenneth B
KB
Department of Medicine, Division of Dermatology, Loyola University Medical Center, Maywood, IL 60153, USA. kgordon@lumc.edu
Vaishnaw
Akshay K
AK
O'Gorman
John
J
Haney
Jeff
J
Menter
Alan
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077944:Alefacept; D015331:Cohort Studies; D003196:Computer Graphics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D011993:Recombinant Fusion Proteins; D000077944:Alefacept