Clinical response to alefacept: results of a phase 3 study of intravenous administration of alefacept in patients with chronic plaque psoriasis

ABSTRACT Background There is a current lack of safe and effective psoriasis therapies that provide patients with lasting remissions after treatment is discontinued. Alefacept, a novel and selective biological agent, has demonstrated durable efficacy in patients with chronic plaque psoriasis, and its efficacy has been correlated with reductions in memory‐effector T cells. Objective To demonstrate the efficacy and safety of both one and two 12‐week courses of alefacept 7.5 mg given once weekly as an intravenous (IV) bolus injection in patients with chronic plaque psoriasis. Methods Multicentre (51 centres in the USA and Canada), randomized, double‐blind, parallel‐group study comparing once‐weekly alefacept 7.5 mg IV or placebo for two 12‐week treatment courses. Each course had a 12‐week follow‐up phase. Patients were eligible for enrolment if they were ≥16 years of age, had chronic plaque psoriasis for ≥12 months involving ≥10% body surface area, and had CD4+ T‐cell counts at or above the lower limit of normal. Results 553 patients received treatment in Course 1, and 449 were treated in Course 2. The cohorts were well balanced for demographic and baseline disease characteristics. During the treatment and follow‐up period of Course 1, 28% of patients treated with alefacept achieved ≥75% reduction in Psoriasis Area and Severity Index (PASI), compared with 8% of placebo‐treated patients ( P < 0.001). Patients achieving ≥75% reduction in PASI following a single 12‐week course of alefacept maintained ≥50% reduction in PASI for a median of over 7 months. Among patients who received a second course of alefacept therapy, 71% achieved ≥50% reduction in PASI, and 40% achieved ≥75% reduction in PASI over two treatment courses. One or two 12‐week courses of alefacept were similarly well tolerated. Conclusions Treatment with alefacept 7.5 mg IV provided highly significant improvements in all measures of psoriasis disease activity compared with placebo. A second course of alefacept provided additional benefit.