title: Efficacy of bypassing agents in patients with hemophilia and inhibitors: a systematic review and meta-analysis.
abstract: BACKGROUND
  Activated prothrombin complex concentrate (aPCC) and recombinant Factor VIIa (rFVIIa) are 2 bypassing agents commonly used for treating acute bleeds in hemophiliac patients with inhibitors. A wide range of efficacy rates for aPCC and rFVIIa have been reported in a number of single-armed and randomized controlled comparative studies.
  
  
  OBJECTIVE
  The aims of this study were to compare the clinical efficacy of aPCC and rFVIIa using a classic meta-analytic approach and to explore the role of study characteristics as covariates in a meta-analysis of previously published clinical studies in hemophiliac patients with antibodies to the missing Factor VIII or IX.
  
  
  METHODS
  A systematic search was conducted to identify studies on the efficacy of aPCC and rFVIIa 90 and 270 μg/kg for treating joint bleeds. The efficacy rates with aPCC and rFVIIa were pooled separately, assuming fixed or random effects. Subgroup analyses were conducted to pool the efficacy rates for bleeds evaluated at 8-12, 18-27, and 36-72 hours after the start of the initial infusion. Meta-regression was used to investigate the association between pooled efficacy rates and study characteristics.
  
  
  RESULTS
  Although only 2 studies directly compared the efficacy of aPCC and rFVIIa, data from ~2392 joint bleeding episodes from 19 studies were included. The pooled efficacy rates were 80.8% with aPCC and 68.4% with rFVIIa (90 μg/kg, 72.0%; 270 μg/kg, 55.7%). The pooled efficacy rates with aPCC at 8-12, 18-27, and 36-72 hours were 49.2%, 70.2%, and 90.9%, respectively. The corresponding pooled rates with rFVIIa 90 μg/kg were 66.6%, 70.7%, and 77.7%. No significant differences were found between the pooled efficacy rates with aPCC and rFVIIa overall or at any of the time points evaluated. Positive associations were found between reported efficacy and duration of follow-up and the number of bleeds evaluated.
  
  
  CONCLUSIONS
  Given the paucity of high-quality studies, the findings from the present review and meta-analysis suggest no conclusive evidence that aPCC or rFVIIa is significantly more efficacious than the other in the treatment of joint bleeding episodes in hemophiliac patients with inhibitors.
authors.affiliation: Department of Clinical Pharmacy, Pharmaceutical Economics and Policy, Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, California 90089-7273, USA.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Zhou
authors.forename: Joel W
authors.initials: JW
authors.lastname: Hay
mesh_terms: D000906:Antibodies / Q000097:blood; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D005164:Factor IX / Q000276:immunology; D005169:Factor VIII / Q000276:immunology; D015942:Factor VIIa / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; D005169:Factor VIII; D005164:Factor IX; C103587:recombinant FVIIa; D015942:Factor VIIa