title: Biological treatments for moderate-to-severe psoriasis: indirect comparison.
abstract: OBJECTIVE
  Psoriasis is a chronic skin disease for which there is an increasing range of treatment options. Biological agents (ustekinumab, adalimumab, infliximab and etanercept) are indicated for moderate-to-severe plaque-type psoriasis in adults who fail to respond to, have a contraindication to, or are intolerant to other systemic therapies including cyclosporine, methotrexate and PUVA Unfortunately, with new drugs, the pivotal trials leading to their licensing are often placebo-controlled trials rather than comparative trials vs. established therapies. Therefore, inference on comparative effectiveness of the newer agents must be derived indirectly, through estimation of effects of the new agents vs. a common comparator. The objective of this study is to compare the relative efficacy of the biological agents through a systematic review of the indirect clinical trial evidence.
  
  
  METHODS
  A systematic literature search was performed for clinical trials of biological agents in psoriasis. Pivotal, randomized, double-blind, controlled (placebo) trials using intention-to-treat analysis were selected for detailed analysis. Trials must include PASI 75 as a primary end point. The indirect comparison was performed using the method of Bucher adjusted with the ITC calculator (Indirect Treatment Comparisons of the Canadian Agency for Drugs and Technologies in Health), etanercept being the reference drug. We defined delta value for therapeutic equivalence as a difference in the efficacy of 25% among the different treatment options.
  
  
  CONCLUSIONS
  Fourteen studies (four for ustekinumab, three for adalimumab, three for infliximab and four for etanercept) were included. The indirect comparison results reveal that ustekinumab, adalimumab and infliximab were statistically superior to etanercept with an absolute risk difference for PASI 75 of 12% (95% CI = 5·9-18%), 11% (95% CI = 5·3-16·7%) and 24% (29·7-18·3%) respectively. However, in all situations, the 95% confidence interval does not achieve clinical relevance as no delta exceeds the previously set value (25%).
  
  
  CONCLUSIONS
  Ustekinumab, adalimumab, infliximab and etanercept can be regarded as clinical equivalents for the treatment of psoriasis. Choice between these agents therefore depends on their relative safety profiles, individual contra-indications and cost effectiveness.
authors: Andalusian Public Foundation for the Management of Health Research, Sevilla, Spain. mercedes.galvan.sspa@juntadeandalucia.es
authors: M
authors: M
authors: Galván-Banqueri
authors: R
authors: R
authors: Marín Gil
authors: B
authors: B
authors: Santos Ramos
authors: F J
authors: FJ
authors: Bautista Paloma
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001685:Biological Factors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D057186:Comparative Effectiveness Research / Q000379:methods; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D013810:Therapeutic Equivalency; D000069549:Ustekinumab
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001685:Biological Factors; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000069549:Ustekinumab; D000068879:Adalimumab; D000068800:Etanercept