Efalizumab for patients with moderate to severe chronic plaque psoriasis: results of the international randomised, controlled phase III clinical experience acquired with raptiva (clear) trial.

Psoriasis is a chronic immune-mediated skin condition that requires treatment over decades. No curative agents are available, and long-term administration of the most effective systemic agents or phototherapy is generally limited due to toxicity. Efalizumab is a recombinant humanised monoclonal IgG1 antibody that inhibits key T-cell processes that contribute to the pathogenesis of plaque psoriasis. Previous clinical trials of efalizumab have demonstrated the efficacy, safety and tolerability of efalizumab for treating moderate to severe chronic plaque psoriasis. The present Phase III trial was designed to further evaluate the safety and efficacy of efalizumab in patients with moderate to severe chronic plaque psoriasis in 54 international centres in Australia, Canada, Europe and Russia. This double-blind, placebo-controlled trial randomised 793 patients in a 2:1 ratio to receive subcutaneous efalizumab 1 mg/kg monotherapy (n¼529) or placebo (n¼264) weekly for 12 weeks. This included 526 ‘‘high need’’ patients (342 randomized to efalizumab, 184 to placebo) for whom at least 2 systemic therapies were unsuitable due to lack of efficacy, intolerance or contraindication. Efficacy analyses were performed on the intent-to-treat population (n¼793); safety analyses were performed on the as-treated population (n¼793). Efficacy and safety endpoints are discussed herein; health-related quality-of-life endpoints are discussed in another abstract. At week 12, significantly more efalizumab-treated patients than placebo achieved the primary endpoint, X75% improvement from baseline in their Psoriasis Area and Severity Index (PASI-75; 31% vs 4%, Po.001). At week 12, 54% and 14% of efalizumab-treated and placebo patients, respectively, achieved a 50% PASI improvement PASI. Significantly more efalizumab-treated patients than placebo (27% vs 4%, Po.001) achieved a static Physician’s Global Assessment of ‘‘excellent’’ or ‘‘clear’’ at week 12, the main secondary endpoint. At week 12, the mean percent PASI improvement was 48% in the efalizumab group (vs 9% placebo, P o.001) with statistically significant differences between the treatment groups noted at week 2. Adverse events were generally mild to moderate in severity. The most commonly reported events (X5% of patients in either group) in efalizumab-treated and placebo patients included headache (26% and 14%), ‘influenza-like illness’ (10% and 7%), pyrexia (8% and 1%), arthralgia (7% and 3%), rigors (5%, both groups), myalgia (6% and 3%), nasopharyngitis (5% and 4%), and pruritus (4% and 6%). The majority of these events reflect the ‘acute adverse events’ associated with the first 1 or 2 doses of efalizumab, defined as headache, chills, fever, nausea, vomiting or myalgia occurring within 48 hours of dosing. These results are generally consistent with results from previous efalizumab studies, providing confirmation of the efficacy and safety in patients with psoriasis. Once weekly efalizumab monotherapy results in substantial improvement, demonstrating significant treatment effects on both clinical and quality-of-life measures with an acceptable safety profile, indicating a favourable benefit:risk ratio in adult patients with moderate to severe plaque psoriasis.