title: Subcutaneous Biological Treatments for Moderate to Severe Psoriasis: Interpreting Safety Data by Network Meta-Analysis.
abstract: BACKGROUND
  When multiple treatments are available, network meta-analysis can synthesize evidence and rank their relative profile in terms of effectiveness and/or safety. We applied this approach to the safety of subcutaneous biologicals used in the treatment of moderate to severe psoriasis.
  
  
  METHODS
  Our literature search covered the articles published from January 2000 to September 2014 and was restricted to randomized controlled trials. The agents eligible for our analysis were subcutaneous biological drugs used in patients with moderate to severe psoriasis. A network meta-analysis was conducted using the Bayesian model. The analysis was aimed to compare the safety of these treatments based on 95 % credible intervals and to consequently generate a ranking in safety across the treatments. Two safety end-points were considered: any serious adverse events (AE) and any infectious AE. Risk difference was the outcome measure. The analysis estimated 95 % credible intervals for all direct and indirect comparisons as well as the ranking histogram across the treatments which was determined according to model-based probabilistic analysis.
  
  
  RESULTS
  Our literature search selected a total of 13 randomized controlled trials of which three evaluated adalimumab, five ustekinumab (45 and 90 mg), four etanercept (both high-dose and low-dose) and one high-dose etanercept and ustekinumab (45 and 90 mg). For both end-points of any serious AE and any infectious AE, the Bayesian analysis showed no significant difference in all indirect head-to-head comparisons between active agents. For the end-point of any serious AE, the ranking was ustekinumab 45 mg and ustekinumab 90 mg (at the same rank), followed by placebo and by adalimumab and high-dose etanercept (at the same rank). For any infectious AE, the ranking was: low-dose etanercept, placebo, ustekinumab 45 mg and ustekinumab 90 mg, adalimumab and high-dose etanercept.
  
  
  CONCLUSIONS
  Our analysis synthesized the current evidence on the safety of subcutaneous biological treatments for patients with moderate to severe psoriasis and was successful in defining their respective rankings.
authors.affiliation: HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100, Florence, Italy. andrea.messori.it@gmail.com.|HTA Unit, ESTAV Centro, Area Vasta Centro Toscana, Regional Health System, Via Guimaraes 9-11, 59100, Prato, Italy. andrea.messori.it@gmail.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Messori
authors.affiliation: HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100, Florence, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Trippoli
authors.affiliation: HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100, Florence, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Fadda
authors.affiliation: HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100, Florence, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Maratea
authors.affiliation: HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100, Florence, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Marinai