Report
Extended efalizumab therapy improves chronic plaque psoriasis: Results from a randomized phase III trial

https://doi.org/10.1016/j.jaad.2004.09.029Get rights and content

Background

Efalizumab inhibits multiple T-cell–mediated processes.

Objective

To evaluate 12- and 24-week efalizumab therapy for psoriasis.

Methods

In this phase III, randomized, double-blind trial, 498 patients received subcutaneous 1 or 2 mg/kg/wk efalizumab or placebo for 12 weeks. Efalizumab-treated patients who achieved <75% Psoriasis Area and Severity Index improvement (PASI-75) were re-randomized to a second 12-week course of treatment.

Results

At week 12, 39% and 27% of efalizumab-treated patients (1 and 2 mg/kg, respectively) achieved PASI-75 (vs 2% placebo; P < .001, both dose groups). At week 24, an additional 20% of efalizumab-treated patients achieved PASI-75 (vs placebo 7%, P = .018). Efalizumab was well tolerated.

Conclusion

Twelve-week efalizumab treatment resulted in significant improvement; extension of therapy to 24 weeks resulted in additional improvement in patients who initially had not achieved PASI-75. There were no significant changes in safety profile during weeks 13-24.

Section snippets

Patients

The study population included adults 18-70 years of age diagnosed with moderate to severe plaque psoriasis for at least 6 months, with clinically stable disease for at least 3 months before screening. Eligible patients had a PASI ≥12, had a body surface area (BSA) involvement ≥10% at screening, and were candidates for systemic therapy. Additional inclusion and exclusion criteria were similar to those in previous efalizumab studies.25, 26 The investigative sites received Institutional Review

Patient characteristics

At baseline, 498 patients were initially randomized, and 183 efalizumab-treated patients who had not achieved PASI-75 at week 12 were re-randomized to receive efalizumab or placebo (Fig 2). With the exception of a younger mean age in the placebo group, there were no significant differences between the treatment groups at baseline (Table I). There were no statistical differences for demographic and baseline characteristics across treatment groups for patients who were randomized into the

Discussion

The results of this large Phase III, randomized, double-blind, placebo-controlled trial demonstrated that extending efalizumab treatment resulted in further improvement in many patients. Both 12- and 24-week treatment periods of efalizumab resulted in significant clinical improvement on multiple measures of treatment efficacy compared to placebo. Significant improvement was noted at the primary endpoint of 12 weeks, with 39% and 27% of patients in the efalizumab 1 mg/kg and 2 mg/kg groups,

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      Evaluating the course of psoriasis following this forced drug withdrawal, Morell et al.52 conducted a multicenter observational study with 147 patients treated in twelve Spanish hospitals: rebound following withdrawal of efalizumab was observed in 30% (44/142) of patients, and the likelihood of phenomenon was independent of clinical characteristics, duration of treatment or response (responders to treatment or nonresponders), or therapeutic approach used by the dermatologist following suspension (reiterating ‘the common properties of the rebound effect’ initially cited). The authors concluded that “there was a high frequency of rebound following suspension of efalizumab, exceeding the rate reported in pivotal trials.39–45 This is a particularly noteworthy given the large proportion of patients with a good response to treatment and therefore believed to have a better prognosis”.

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    Genentech, Inc. sponsored this clinical research and was the administrative entity for biostatistical review. All of the authors of this report were members of the Efalizumab Study Group.

    Drs Feldman, Gordon, Leonardi, and Menter have received grant/research support from, served as consultants for, and served on the speakers bureau for Genentech, Inc. Dr Papp has received grant/research support from and served as consultant to Genentech, Inc., Xoma LLC, and Serono S.A. Dr Walicke was an employee of and is a stock shareholder in Genentech, Inc. Mr Compton is a stock shareholder in and an employee of Genentech, Inc. Dr Gottlieb has received grant/research support from and served as consultant to Genentech, Inc.

    A complete listing of the principal investigators can be found at the end of this article.

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