Background: To provide safety data for efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods: A 12- week, Phase IIIb, randomized, double-blind, parallel-group, ...Background: To provide safety data for efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods: A 12- week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of efalizumab 1mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results: During 12 weeks of therapy with efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9% , respectively; the incidence of serious adverse events was 1.8% and 3.4% , respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7% , respectively. In the efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), ≥ 50% improvement in PASI (P < 0.001), and a static Physician’ s Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the efalizumab group (P < 0.001). Conclusions: Efalizumab treatment SC for 12weeks was safe,well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis.展开更多
Background: Psoriasis is associated with abnormal plasma lipid metabolism and a high frequency of cardiovascular events. Increased lipid levels are also seen in patients with psoriasis treated with acitretin. Apolipop...Background: Psoriasis is associated with abnormal plasma lipid metabolism and a high frequency of cardiovascular events. Increased lipid levels are also seen in patients with psoriasis treated with acitretin. Apolipoprotein E (ApoE) variants have been linked to hypertriglyceridaemia and hypercholesterolaemia in normal individuals. Two coding single nucleotide polymorphisms at +3937 and +4075 define the three common ApoE alleles e2, e3 and e4. Objectives: To test the hypothesis that particular ApoE polymorphism(s) are associated with psoriasis and that specific ApoE allelic variant(s) may be a marker for predicting disease response to acitretin. Methods: DNA was genotyped for ApoE polymorphisms using a radioactive hybridization technique in cohorts of patients with psoriasis, including patients with chronic plaque psoriasis (CPP, n = 212), guttate psoriasis (GP, n = 94), palmoplantar pustulosis (PPP, n = 101), controls (n = 137), acitretin responders (n =106) and acitretin nonresponders (n = 84). Results: The frequency of the e4 allele (+3937C/+4075C) was significantly higher in patients with CPP and GP than in controls (P = 0.008 and P = 0.02, respectively). There was no significant difference in allele frequencies between patients with PPP and controls. Allelic distribution was similar in acitretin responders and nonresponders. Conclusions: These data demonstrate an association between the Apo e4 allele and CPP and GP, suggesting a possible pathogenic role for ApoE in psoriasis. Our results do not support a link between disease response to acitretin and the e2, e3 or e4 allelic variants of ApoE.展开更多
文摘Background: To provide safety data for efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods: A 12- week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of efalizumab 1mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results: During 12 weeks of therapy with efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9% , respectively; the incidence of serious adverse events was 1.8% and 3.4% , respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7% , respectively. In the efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), ≥ 50% improvement in PASI (P < 0.001), and a static Physician’ s Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the efalizumab group (P < 0.001). Conclusions: Efalizumab treatment SC for 12weeks was safe,well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis.
文摘Background: Psoriasis is associated with abnormal plasma lipid metabolism and a high frequency of cardiovascular events. Increased lipid levels are also seen in patients with psoriasis treated with acitretin. Apolipoprotein E (ApoE) variants have been linked to hypertriglyceridaemia and hypercholesterolaemia in normal individuals. Two coding single nucleotide polymorphisms at +3937 and +4075 define the three common ApoE alleles e2, e3 and e4. Objectives: To test the hypothesis that particular ApoE polymorphism(s) are associated with psoriasis and that specific ApoE allelic variant(s) may be a marker for predicting disease response to acitretin. Methods: DNA was genotyped for ApoE polymorphisms using a radioactive hybridization technique in cohorts of patients with psoriasis, including patients with chronic plaque psoriasis (CPP, n = 212), guttate psoriasis (GP, n = 94), palmoplantar pustulosis (PPP, n = 101), controls (n = 137), acitretin responders (n =106) and acitretin nonresponders (n = 84). Results: The frequency of the e4 allele (+3937C/+4075C) was significantly higher in patients with CPP and GP than in controls (P = 0.008 and P = 0.02, respectively). There was no significant difference in allele frequencies between patients with PPP and controls. Allelic distribution was similar in acitretin responders and nonresponders. Conclusions: These data demonstrate an association between the Apo e4 allele and CPP and GP, suggesting a possible pathogenic role for ApoE in psoriasis. Our results do not support a link between disease response to acitretin and the e2, e3 or e4 allelic variants of ApoE.
