CLinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial |
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Authors: | Dubertret L,Sterry W,Bos J D,Chimenti S,Shumack S,Larsen C G,Shear N H,Papp K A CLEAR Multinational Study Group |
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Affiliation: | H?pital Saint Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France *University Hospital Charite, Berlin, Germany ?Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands ?Clinica Dermatologica, Universita degli Studi di Roma ‘Tor Vergata’, Rome, Italy §St George Dermatology, Kogarah, Australia ?Department of Dermatology, Norwegian University of Science and Technology, Trondheim, Norway **Ventana Clinical Research, Toronto, Ontario, Canada ??Probity Medical Research, Waterloo, Ontario, Canada ??Full investigator list is given at the end of the article |
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Abstract: | BACKGROUND: Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. OBJECTIVES: This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. PATIENTS/METHODS: Patients with moderate-to-severe plaque psoriasis [involvement of >or=10% of total body surface area and Psoriasis Area and Severity Index (PASI)>or=12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving >or=75% PASI improvement (PASI-75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were 29.5% for efalizumab compared with 2.7% for placebo among high-need patients (P<0.0001) and 31.4% for efalizumab compared with 4.2% for placebo in the full study population (P<0.0001). RESULTS: for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high-need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high-need group and the overall study population. CONCLUSIONS: The efficacy and safety of efalizumab therapy were comparable between high-need patients and the more general moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients. |
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Keywords: | anti-CD11a efalizumab high-need patients lymphocyte function-associated antigen (LFA)-1 monoclonal antibody plaque psoriasis |
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