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Development and use of alefacept to treat psoriasis
Gerald G Krueger1, Kristina P Callis
1Department of Dermatology, University of Utah Health Sciences Center, 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 apoptosis 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 > or =75% and nearly 2/3 a reduction in PASI of > or =50%. Patients who achieved a > or =75% reduction from baseline PASI during or after a single course maintained a > or =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 > or =75% and > or =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.
Insights
Alefacept effectively treats psoriasis by targeting pathogenic T cells. Clinical trials show significant, durable skin improvement with a favorable safety profile.
Area of Science:
- Immunology
- Dermatology
- Pharmacology
Background:
- Psoriasis pathogenesis involves activated memory T cells expressing CD2.
- Alefacept targets CD2 to induce apoptosis of pathogenic T cells.
Purpose of the Study:
- To present safety and efficacy data for alefacept's New Drug Application (NDA) for psoriasis treatment.
- Evaluate alefacept's effectiveness in reducing psoriasis severity.
Main Methods:
- Review of Phase II and III clinical trials involving over 1300 patients.
- Administration of 12 weekly intramuscular or intravenous injections of alefacept.
- Assessment of Psoriasis Area and Severity Index (PASI) scores during treatment and follow-up.
Main Results:
- Approximately one-third of patients achieved >=75% PASI reduction; nearly two-thirds achieved >=50% PASI reduction.
- A >=75% PASI reduction was maintained for over 7 months in some patients after one course.
- Two courses of alefacept improved efficacy and prolonged duration of effect, with 40% achieving >=75% PASI reduction.
Conclusions:
- Alefacept demonstrates significant efficacy in improving psoriasis symptoms.
- The drug offers durable clinical improvement with a favorable safety profile.
- Adverse events were comparable between alefacept and placebo groups.