title: Biological drugs for the treatment of moderate-to-severe psoriasis by subcutaneous route: determining statistical equivalence according to evidence-based methods.
abstract: BACKGROUND
  Although several evidence-based analyses have found that in patients with moderate-to-severe psoriasis, biological agents for subcutaneous use show no difference in efficacy (no proof of difference), there is limited evidence on whether or not there is also proof of no difference.
  
  
  METHODS
  The clinical material was the same as that reported in previous meta-analyses. Our methodology was a combination of meta-analysis and equivalence testing. The endpoint was the rate of Psoriasis Area and Severity Index (PASI) 75 achievement. The agents examined for equivalence testing included etanercept, high-dose etanercept, adalimumab, ustekinumab, and high-dose ustekinumab. The equivalence margin [±18 % as risk difference (RD)] was derived from statistical power information from the original trials; a more conservative margin at ±10 % was also tested.
  
  
  RESULTS
  Our analysis involved 16 randomized trials including 8,257 patients. Ten head-to-head indirect comparisons were made and the respective values of RD were estimated. The 95 % confidence intervals for RDs remained within the margins of ±18 and ±10 % in six and two cases, respectively. A post hoc margin of about ±25 % was satisfied in all cases. All analyses assumed α = 2.5 %.
  
  
  CONCLUSIONS
  Our study indicates that some of these five biological treatments can be equivalent, but results are strongly influenced by the margins adopted. Our findings can be helpful to develop local acquisition tenders on these drugs.
authors: HTA Unit, Area Vasta Centro Toscana Regional Health System, Via San Salvi 12, 50100, Florence, Italy, andrea.messori.it@gmail.com.
authors: Andrea
authors: A
authors: Messori
authors: Valeria
authors: V
authors: Fadda
authors: Dario
authors: D
authors: Maratea
authors: Sabrina
authors: S
authors: Trippoli
authors: Roberta
authors: R
authors: Gatto
authors: Mauro
authors: M
authors: De Rosa
authors: Claudio
authors: C
authors: Marinai
mesh_terms: D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics; D001685:Biological Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000068800:Etanercept; D019317:Evidence-Based Medicine / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000378:metabolism; D007279:Injections, Subcutaneous; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000378:metabolism; D012720:Severity of Illness Index; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D000069549:Ustekinumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001685:Biological Factors; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069549:Ustekinumab; D000068879:Adalimumab; D000068800:Etanercept