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
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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DOI：
10.1111/j.1365-2133.2006.07344.x
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发表时间：
2006-07-01
影响因子：
10.3
通讯作者：
Papp, K. A.
中科院分区：
文献类型：
--
作者：
Dubertret, L.;Sterry, W.;Papp, K. A.
背景依法利珠单抗（抗-CD11a），一种人源化单克隆抗体，阻断银屑病发病机制中涉及的多种T细胞依赖性功能，包括T细胞活化、向皮肤迁移、银屑病皮肤中的再活化以及与角质形成细胞的相互作用。一项平行组试验旨在评估皮下注射依法利珠单抗1.0 mg kg（-1），每周一次，持续12周，与安慰剂相比，在包括高需求患者的人群中的安全性和有效性，患者/方法将患有中度至重度斑块状银屑病[在筛选时累及全身表面积>= 10%且银屑病面积和严重性指数（PASI）>= 12.0]的患者随机分为2组：接受依法利珠单抗或安慰剂的比例为1。主要疗效终点是PASI改善≥ 75%的患者比例（PASI-75应答）;次要终点包括PASI的变化，静态医生总体评估，医生对从基线的变化和受影响的体表面积百分比的总体评估。（529例接受依法利珠单抗治疗，264例接受安慰剂治疗），包括526例高需求患者（342例接受依法利珠单抗治疗，184例接受安慰剂治疗）。在高需求患者中，依法利珠单抗组第12周PASI-75发生率为29.5%，安慰剂组为2.7%（P <0.0001），在整个研究人群中，依法利珠单抗组为31.4%，安慰剂组为4.2%（P <0.0001）。所有次要疗效终点的结果显示，在高需求人群和全人群中，依法利珠单抗均优于安慰剂。依法利珠单抗表现出良好的安全性，没有全身毒性的证据，在高需求组和整体studypopulation.Conclusion依法利珠单抗治疗的疗效和安全性之间的高需求的患者和更普遍的中重度银屑病患者人群相媲美。鉴于其已证实的疗效和安全性特征，依法利珠单抗是治疗中重度斑块状银屑病成人患者（包括高需求患者）的一种有价值的选择。
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 >= 10% of total body surface area and Psoriasis Area and Severity Index (PASI) >= 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 >= 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.Conclusion 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.