BACKGROUND: The comparative effects of biological response modifiers (BRMs) on the severity of psoriasis and its effects on health-related quality of life (HRQoL) have not been evaluated. OBJECTIVE: To conduct a meta-analysis to assess the effects of available biological agents on the severity of psoriasis, as well as to provide data on the effects of these agents on HRQoL. METHODS: Medline and other databases were searched for randomized controlled trials (>or= 10 weeks' duration in adults) comparing biological therapies for moderate-to-severe psoriasis with placebo. A Mantel-Haenszel fixed-effects model was employed to estimate the pooled relative risks (RR) of patients achieving >or= 75% reduction of baseline Psoriasis Area and Severity Index (PASI 75) after >or= 10 weeks of treatment. Similar analyses were also conducted on PASI 50 and PASI 90. Using a random-effects model, we estimated the likelihood of achieving PASI 50, PASI 75, and PASI 90 at 10-12 weeks and 24 weeks. Data on the effects of different BRMs (vs. placebo) on HRQoL were also presented. Numbers (%) of patients discontinuing treatment were presented as a general index of drug tolerability. RESULTS: Patients receiving infliximab 5 mg/kg intravenously at weeks 0, 2, and 6, then every 8 weeks, had the highest RR of achieving PASI 75, with a pooled RR value of 25.48 (95% confidence interval [CI], 14.04-46.23); followed by etanercept 50 mg administered subcutaneously (SC) twice weekly with RR = 11.92 (95% CI, 8.17-17.39); etanercept 25 mg SC twice weekly with RR = 10.68 (95% CI, 6.15-18.57); efalizumab 1-2 mg/kg SC per week with RR = 7.47 (95% CI, 5.20-10.73); and alefacept administered weekly (various doses) with RR = 3.37 (95% CI, 2.18-5.23). (All RR values were estimated vs. placebo.) Similar findings were observed with regard to proportions of patients achieving PASI 50 and PASI 90. The random-effects analysis suggested that infliximab significantly increased the likelihood of achieving PASI 50, PASI 75, and PASI 90 compared with placebo at 10-12 weeks; however, there were no significant differences between biological treatments at 24 weeks. Each BRM improved HRQoL compared with placebo according to findings from the Dermatology Life Quality Index. Proportions of patients discontinuing treatment were similar in active-treatment and placebo groups. CONCLUSIONS: Infliximab significantly reduced disease severity by both fixed- and random-effects models. All biological therapies improved HRQoL compared with placebo, and proportions of patients discontinuing treatment were similar in active-treatment and placebo groups. The analysis is potentially limited by statistical factors and did not systematically account for different toxicity profiles, but the findings establish a foundation for head-to-head comparative trials.