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Abstract 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. With a prevalence of about 2–3% in the general population, psoriasis is one of the most common immune-mediated disorders.1 Currently incurable, psoriasis causes remarkable direct costs, work limitations and productivity loss.2–5 Among several clinical phenotypes, chronic plaque psoriasis is most frequent and accounts for about 90% of cases.1,2 Psoriasis may cause substantial problems in everyday life.6 Recently, several studies suggested that patients with severe psoriasis have an increased risk for cardiovascular disease, depressive illness, and a decreased life expectancy.7–12 Systemic treatments are limited to patients with moderate-to-severe psoriasis in whom the activity of skin lesions and concurrent symptoms cannot be sufficiently controlled with topical treatments and with phototherapy. Conventional systemic agents approved for chronic plaque psoriasis include ciclosporin, methotrexate, fumaric acid esters and acitretin (primarily indicated in severe palmoplantar pustulosis).13–15The recognition of the central role of T cells and tumour necrosis factor (TNF)-α in the pathogenesis of psoriasis led to the development of new biologic treatments. Currently, three biologic TNF-α inhibitors (infliximab,16 etanercept17 and adalimumab18) and two T-cell agents (efalizumab19 and alefacept20) are approved for chronic plaque psoriasis. Relevant summaries of product characteristics and national treatment guidelines applicable in Europe (but not in the U.S.A.) recommend these biologic agents as a second-line therapy for patients with moderate-to-severe psoriasis who have failed to respond to conventional nonbiologic agents, have become intolerant to conventional systemic therapy, and/or cannot receive conventional systemic therapy because of an increased risk of developing clinically relevant drug-related toxicity.14,15,21 To date, however, the different biologic and prebiologic systemic treatment options for chronic plaque psoriasis have not yet been compared against each other according to the principles of evidence-based medicine. We undertook a systematic review and meta-analysis of all published randomized controlled trials (RCTs) of biologic and nonbiologic systemic treatments approved for moderate-to-severe plaque psoriasis to determine their comparative efficacy and tolerability. |