Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials.
BACKGROUND
The comparative efficacy and tolerability of conventional and biologic treatments for moderate-to-severe plaque psoriasis are unknown.


OBJECTIVE
To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting efficacy of systemic treatments approved for moderate-to-severe psoriasis by means of the Psoriasis Area and Severity Index (PASI).


METHODS
We identified relevant articles by systematic electronic searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as proportion of participants with >or= 75% decrease in PASI (PASI-75) at primary efficacy measurement (week 8-16). PASI-75 response rates of double-blind placebo-controlled trials were summarized as risk differences (RDs) and pooled using random effects models. Tolerability was assessed from rates of withdrawals and adverse events.


RESULTS
Twenty-four RCTs totalling 9384 patients were analysed qualitatively. Sixteen double-blind placebo-controlled trials were eligible for meta-analysis. Infliximab was significantly superior to all other interventions [RD 77%, 95% confidence interval (CI) 72-81%]. Adalimumab (RD 64%, 95% CI 61-68%) was superior to ciclosporin (RD 33%, 95% CI 13-52%), efalizumab (RD 24%, 95% CI 19-30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40-48%) and etanercept 25 mg twice weekly (RD 30%, 95% CI 25-35%). Efalizumab was significantly less efficacious than fumaric acid esters (RD 48%, 95% CI 32-64%). Rates of withdrawals due to adverse events were highest for methotrexate and fumaric acid esters.


CONCLUSIONS
The efficacy of systemic agents approved for moderate-to-severe psoriasis differs considerably both within and between biologics and nonbiologics. Infliximab is most efficacious, followed by adalimumab. Patients receiving infliximab have an excess chance of 77% over placebo to achieve PASI-75 response. Published evidence questions regulatory guidelines that recommend biologics as second-line therapy for moderate-to-severe plaque psoriasis.
Schmitt
J
J
Department of Dermatology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany. jochen.schmitt@uniklinikum-dresden.de
Zhang
Z
Z
Wozel
G
G
Meurer
M
M
Kirch
W
W
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D011701:PUVA Therapy; D017410:Practice Guidelines as Topic; D011565:Psoriasis / Q000188:drug therapy / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D007166:Immunosuppressive Agents; D000069285:Infliximab; D000068879:Adalimumab