Development and use of alefacept to treat psoriasis - 29/08/11

Doi : 10.1016/mjd.2003.552

Gerald G Krueger, MD ^a,^⁎, Kristina P Callis, MD ^a
^a Department of Dermatology, University of Utah Health Sciences CenterSalt Lake City, Utah, USA

^*Reprint requests: Gerald G. Krueger, MD, Department of Dermatology, 4B454 School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132-2409, USA

Abstract

Activated memory T cells, expressing CD2, are key components in the pathogenesis of psoriasis. Alefacept binds to CD2, blocks co-stimulatory signaling, and selectively induces apotosis of pathogenic T cells. Our objective is to present safety and efficacy results which lead to the new drug application (NDA) of alefacept for the treatment of psoriasis. We reviewed the key phase II and III trials in over 1300 patients and found that during treatment and follow-up of patients receiving 12 weekly intramuscular or intravenous injections of alefacept, about 1/3 will achieve a reduction in psoriasis area and severity index (PASI) of ≥75% and nearly 2/3 a reduction in PASI of ≥50%. Patients who achieved a ≥75% reduction from baseline PASI during or after a single course maintained a ≥50% reduction in PASI for a median duration of >7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a ≥75% and ≥50% reduction in PASI, respectively and duration of effect was prolonged. Adverse events in the placebo and active treatment arms did not differ. We conclude that alefacept significantly improves psoriasis and produces durable clinical improvement with a very favorable safety profile.

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Plan

Reasons for a new approach to treat psoriasis

Psoriasis is a T cell–mediated disease and molecular definition of T cell–mediated immune responses leads to a rationally based therapy

Mechanism of action of alefacept

Summary of pivotal clinical trials with alefacept

Efficacy

Duration of response with IV and IM alefacept

Safety and tolerability

Common questions on the clinical use of alefacept

How should the clinician and patient interpret the clinical response data generated in the clinical trials conducted on patients with “moderate to severe” disease?

Who should be treated with alefacept?

Is there a preference for IV or IM alefacept administration?

What is the most effective way to assess improvement?

Who should get a second course and is a 12-week observation period necessary after each course?

When should the next course be given?

Is it safe to increase the dose?

What other agents are predicted to be compatible with alefacept and how and when should they be used?

What laboratory testing is required for patients being treated with alefacept?

How should alefacept be used in subsets of patients in whom there is no clinical trial experience?

Summary

Funding sources: Alefacept studies cited herein were funded by Biogen, Inc.
Disclosure: Much of this review comes from a chapter for a book entitled Therapy for Moderate to Severe Psoriasis, commissioned by the National Psoriasis Foundation and edited by Gerald D. Weinstein and Alice B. Gottlieb, 2003. A patent on the use of alefacept for the treatment of psoriasis has been assigned to Biogen, Inc and the University of Michigan. Neither of the authors have a financial interest in the patent. Dr Krueger is a consultant to Biogen, as well as to other companies that have and are developing treatments for psoriasis. Dr Callis was a clinical research fellow during the writing of this manuscript and did not receive any financial support from Biogen.