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Alefacept Therapy May Result In Prolonged Psoriasis Remission Through Reduction Of T-Cell Subsets

Alefacept therapy reduces levels of circulating memory T-cell subsets in patients with psoriasis and can lead to prolonged disease remission, research in North America indicates.

One or 2 courses of intravenous alefacept reduced CD4⁺ and CD8⁺ memory T-cell counts in a study of 553 psoriasis patients, 16 years or older, who had moderate-to-severe, stable plaque psoriasis for at least 12 months. Their disease involved at least 10% of body surface area, and patients had normal CD4⁺ lymphocyte counts. Participants were treated at 51 study centres in the United States and Canada.

"The reduction in levels of circulating memory T-cell subsets with alefacept treatment correlates to improvement in psoriasis and suggests a relationship between the length of response to alefacept and alterations in the memory T-cell population," report researchers led by Dr. Kenneth Gordon of Loyola University Medical Centre in Maywood, Illinois, United States.

They explain that scientific and clinical evidence had already pointed to a pivotal role for the T-cell in psoriasis. Their data "strongly" support this central role of memory T-cells, as well as the potential efficacy advantages of targeting effector cells in treating the disease.

Participants were randomised to 1 of 3 cohorts on a 1:1:1 basis. Cohort 1 received 7.5 milligrams of alefacept in both of 2 drug courses; cohort 2 took 7.5 mg of alefacept in the first and placebo in the second course. Cohort 3 took placebo in the course and 7.5 mg of alefacept in the second course.

Nine treatments were prohibited within 4 weeks of alefacept administration and during the study: phototherapy, systemic retinoids, systemic steroids, systemic fumarates, methotrexate, cyclosporine, azathioprine, thioguanine or high-potency topical corticosteroids. Moderate-potency topical corticosteroids, vitamin D analogues, keratolytics and coal tar use were prohibited within 2 weeks of drug administration and throughout the study, except on the scalp, palms, groin, anal fold and soles.

Except within 12 hours of efficacy assessments, sparing use of low-potency topical corticosteroids and emollients was permitted.

At 12 weeks following the last course 1 alefacept dose, 88% of patients had CD4⁺ cell counts greater than the lower normal limit. At 12 weeks following the last course 2 alefacept dose, 83% of patients had reached this marker.

Patients with the largest decreases in memory T-cell counts through course 1 alefacept therapy experienced the greatest reductions in disease activity
Archives of Dermatology 2003;139:1563-1570.

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