Background: Efalizumab (anti-CD11a), a humanized monoclonalantibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactiva...Background: Efalizumab (anti-CD11a), a humanized monoclonalantibody, 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 moderateto- 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. Conclusions: The efficacy and safety of efalizumab therapy were comparable between high-need patients and themore 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.展开更多
LFA-1, a member of 2 integrin family, plays important roles in immune cell adhesion, trafficking and activation. LFA-1 is present on all leukocytes and is a therapeutic target
文摘Background: Efalizumab (anti-CD11a), a humanized monoclonalantibody, 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 moderateto- 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. Conclusions: The efficacy and safety of efalizumab therapy were comparable between high-need patients and themore 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.
文摘LFA-1, a member of 2 integrin family, plays important roles in immune cell adhesion, trafficking and activation. LFA-1 is present on all leukocytes and is a therapeutic target
