Incidence of infection during efalizumab therapy for psoriasis: Analysis of the clinical trial experience

• Published in: Clinical therapeutics Vol. 27; no. 9; pp. 1317 - 1328
• Main Authors: Langley, Richard G.B., Carey, Wayne P., Rafal, Elyse S., Tyring, Stephen K., Caro, Ivor, Wang, Xiaolin, Wetherill, Graham, Gordon, Kenneth B.
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 01-09-2005; Excerpta Medica; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Dermatology; efalizumab; Female; Humans; immune system; Incidence; infection; Infection - epidemiology; Infection - etiology; Male; Medical sciences; Middle Aged; monoclonal antibody; Pharmacology. Drug treatments; psoriasis; Psoriasis - classification; Psoriasis - drug therapy; Psoriasis. Parapsoriasis. Lichen; Randomized Controlled Trials as Topic; safety; Time Factors; immune system; infection; monoclonal antibody; efalizumab; psoriasis; safety; Human; Skin disease; Psoriasis; Toxicity; Antipsoriatic agent; Monoclonal antibody; Efalizumab; Epidemiology; Incidence; Immunomodulator; Infection; Treatment; Clinical trial; Safety; Immune system
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2005.09.007

Abstract
Because many therapies for psoriasis disrupt the normal inflammatory cascade and could theoretically impair the body's ability to respond to external pathogens, a possible increase in the incidence of infection is a concern with any new psoriasis therapy that affects the immune system. Efalizumab is a biologic therapy targeted to inhibit T cells. Its efficacy has been shown in clinical trials encompassing >3500 patients with psoriasis.
The aims of this article were to review the incidence of infection observed in efalizumab-treated patients during 12-week, Phase III clinical trials, compare the incidence rate with that in patients receiving placebo, and evaluate the incidence of infection observed in patients with extended (>12-week) efalizumab use.
Adverse events (AEs) of infection were tabulated from a pooled data set of 2335 patients enrolled to receive 12 weeks of subcutaneous (SC) efalizumab 1 or 2 mg/kg · wk or placebo in 4 randomized, double-blind, placebo-controlled, Phase III efalizumab clinical studies. The incidence of infection was further evaluated using pooled data from 1115 patients who received up to 24 weeks of efalizumab therapy during 5 clinical trials with treatment extension arms and from 170 patients who received up to 108 weeks (27 months) of continuous therapy in an open-label, Phase III efalizumab trial of 36 months' total duration.
The incidence and severity of AEs of infection during 12 weeks of efalizumab therapy were comparable to those observed in patients receiving placebo (overall, 28.6% vs 26.3%). Infections did not appear to increase with extended therapy of up to 27 months. Serious infections requiring hospitalization occurred in 1.1% of efalizumab-treated patients.
The present review of the available Phase III clinical trial suggests that efalizumab is not associated with an increased risk for infection in patients receiving initial or long-term (27-month) treatment for moderate to severe chronic plaque psoriasis.