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

Authors: Hamilton, Tiffani¹; Menter, Alan²; Caro, Ivor³; Compton, Peter³; Sobell, Jeffrey⁴; Papp, Kim A.⁵

Source: Drug Safety, Volume 31, Number 8, 2008 , pp. 715-726(12)

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Abstract:

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, 37-48 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 infection ranged from 9.9% to 14.7% during the 12-week segments of efalizumab therapy, compared with an incidence of 19.1% for placebo-treated patients. Malignancies were reported with an incidence of ≤1.0% for efalizumab-treated patients during any 12-week segment compared with 0.4% for the 12-week placebo-treated patients. Of the 15 malignancies reported for efalizumab-treated patients, 13 were basal cell (n = 4) or squamous cell (n = 9) carcinomas.

Conclusions: These results support the short-term safety profile demonstrated for efalizumab over a longer-term therapy period of up to 60 weeks.

Keywords: Efalizumab; Psoriasis

Document Type: Research article

Affiliations: 1: 1 Atlanta Dermatology, Vein & Research Center, Atlanta, Georgia, USA 2: 2 Baylor Research Institute, Dallas, Texas, USA 3: 3 Genentech Inc., San Francisco, California, USA 4: 4 SkinCare Physicians, Chestnut Hill, Massachusetts, USA 5: 5 Probity Medical Research, Waterloo, Ontario, Canada

Publication date: 2008-01-01

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

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