Safety of Efalizumab Therapy in Patients with Moderate to Severe Psoriasis: An Open-Label Extension of a Phase IIIb Trial

• Published in: Drug safety 2008-01, Vol.31 (8), p.715-726
• Main Authors: Hamilton, Tiffani, Menter, Alan, Caro, Ivor, Compton, Peter, Sobell, Jeffrey, Papp, Kim A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Dermatology; Drug Safety and Pharmacovigilance; Drug toxicity and drugs side effects treatment; Female; Follow-Up Studies; Humans; Incidence; Infection - epidemiology; Infection - etiology; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Neoplasms - chemically induced; Neoplasms - epidemiology; Original Research Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Psoriasis - drug therapy; Psoriasis. Parapsoriasis. Lichen; Severity of Illness Index; Time Factors; Young Adult
• ISSN: 0114-5916; 1179-1942
• DOI: 10.2165/00002018-200831080-00008

Background: Psoriasis is a chronic autoimmune disease characterized by infiltration of the dermis and epidermis by activated T cells and the hyperproliferation and abnormal differentiation of keratinocytes. It is a life-long disease with alternating periods of remission and recurrence. Efalizumab is a humanized, recombinant, T-cell targeting monoclonal antibody, approved for use in adults with chronic moderate to severe plaque psoriasis. Objective: To assess the safety of continued or newly initiated treatment with efalizumab for up to 48 weeks in patients with psoriasis who were treated previously with efalizumab or placebo. Methods: This study was an open-label, 48-week extension of a previously published 12-week, randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase IIIb study, carried out in the US and Canada between 24 October 2002 and 2 July 2004. Patients were followed and treated at the study clinic in an outpatient setting and also were trained to self-administer the drug at home. Patients comprising individuals with chronic moderate to severe plaque psoriasis who had completed the 12-week, placebo-controlled segment of the study were eligible for enrolment in the extension phase. Of the 686 patients enrolled in the study, 636 (92.7%) enrolled in the open-label extension of the study, 418 of whom had received 12 weeks of efalizumab therapy and 218 of whom had received 12 weeks of placebo. All patients entering the open-label phase of the study received efalizumab 1 mg/kg/wk for an additional 48 weeks, for a maximum exposure of up to 60 weeks. Safety was evaluated by an assessment of adverse events, including infections and serious adverse events. Results: The rate of withdrawal due to adverse events remained low throughout the trial, ranging from 1.2% to 6.6% during the 12-week segments of the open-label extension phase of the trial. The incidence of adverse events decreased with increased exposure to efalizumab; the incidence during the initial 12 weeks of exposure to efalizumab was 79.0% compared with 72.9% for patients exposed to placebo. Patients treated with efalizumab for 13–24 weeks, 25–36 weeks, 37–8 weeks and 49–60 weeks experienced adverse events at an incidence of 66.8%, 54.3%, 49.6% and 48.5%, respectively. The incidence of serious adverse events ranged from 1.6% to 3.5% during the 12-week segments of efalizumab therapy, compared with an incidence of 3.4% for placebo-treated patients. The incidence of infecti