Safety of efalizumab therapy in patients with moderate to severe psoriasis: an open-label extension of a phase IIIb trial.

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.

• Authors: Tiffani Hamilton, Alan Menter, Ivor Caro, Peter Compton, Jeffrey Sobell, Kim A Papp
• Journal: Drug safety (Drug Saf) Vol. 31 Issue 8 Pg. 715-26 ( 2008) ISSN: 0114-5916 [Print] New Zealand
• PMID: 18636790 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• efalizumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Female
• Follow-Up Studies
• Humans
• Incidence
• Infections (epidemiology, etiology)
• Male
• Middle Aged
• Neoplasms (chemically induced, epidemiology)
• Psoriasis (drug therapy)
• Severity of Illness Index
• Time Factors
• Young Adult