Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes.

Abstract

BACKGROUND:

Psoriatic plaques are characterized by infiltration with CD4+ CD45RO+ and CD8+ CD45RO+ memory effector T lymphocytes. The recombinant protein alefacept binds to CD2 on memory effector T lymphocytes, inhibiting their activation.

METHODS:

In a multicenter, randomized, placebo-controlled, double-blind study, we evaluated alefacept as a treatment for psoriasis. Two hundred twenty-nine patients with chronic psoriasis received intravenous alefacept (0.025, 0.075, or 0.150 mg per kilogram of body weight) or placebo weekly for 12 weeks, with follow-up for 12 additional weeks. Before treatment, the median scores on the psoriasis area-and-severity index were between 14 and 20 in all groups (0 denotes no psoriasis and 72 the most severe disease possible).

RESULTS:

Alefacept was well tolerated and nonimmunogenic. The mean reduction in the score on the psoriasis area-and-severity index two weeks after treatment was greater in the alefacept groups (38, 53, and 53 percent in the groups receiving 0.025, 0.075, and 0.150 mg per kilogram, respectively) than in the placebo group (21 percent, P<0.001). Twelve weeks after treatment, 28 patients who had received alefacept alone were clear or almost clear of psoriasis. Three patients in the placebo group were clear or almost clear; all three had received additional systemic therapy for psoriasis. Alefacept reduced peripheral-blood memory effector T-lymphocyte (CD45RO+) counts, and the reduction in the number of memory-effector T lymphocytes was correlated with the improvement in psoriasis.

CONCLUSIONS:

Treatment with alefacept for 12 weeks is associated with improvement in chronic plaque psoriasis; some patients have a sustained clinical response after the cessation of treatment. Alefacept selectively targets CD45RO+ memory effector T lymphocytes, suggesting that they have a role in the pathogenesis of psoriasis.

• Authors: C N Ellis, G G Krueger, Alefacept Clinical Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 345 Issue 4 Pg. 248-55 (Jul 26 2001) ISSN: 0028-4793 [Print] United States
• PMID: 11474662 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Recombinant Fusion Proteins
• Leukocyte Common Antigens
• Alefacept

Topics

• Adjuvants, Immunologic (adverse effects, pharmacology, therapeutic use)
• Adolescent
• Adult
• Aged
• Alefacept
• Chronic Disease
• Double-Blind Method
• Female
• Humans
• Leukocyte Common Antigens
• Lymphocyte Count
• Male
• Middle Aged
• Psoriasis (drug therapy, immunology)
• Recombinant Fusion Proteins (adverse effects, immunology, pharmacology, therapeutic use)
• Severity of Illness Index
• T-Lymphocytes (drug effects, immunology)
• Time Factors
• Treatment Outcome