title: Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors.
abstract: BACKGROUND
  The primary treatment for mild-to-moderate bleeding disorders in hemophilia is either recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (aPCC). The efficacy of both products has been evaluated in individual studies; however, there has not been an overall review to compare the efficacy from these individual studies of rFVIIa and aPCC. Our aim is to establish robust estimates of the efficacy, speed of bleed resolution, and adverse event profile of both rFVIIa and aPCC.
  
  
  METHODS
  A systematic review was conducted of the relevant literature.
  
  
  RESULTS
  We identified 11 open-label cohort studies, six randomized clinical trials, including two head-to-head clinical trials, and a meta-analysis. The definition of efficacy varies between these studies, but is usually a composite measure of definite pain relief, reduction in the size of the hemorrhage, and cessation of bleeding. The individual making the interpretation of efficacy and the time from treatment initiation to recording the efficacy endpoint also varies across the studies. Overall, estimates of efficacy from randomized clinical trials using dosing regimens in line with the guidelines are higher for rFVIIa (81%-91%) than for aPCC (64%-80%). Conclusions from a meta-analysis suggest that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than aPCC due to higher efficacy levels at different time points. The results from a comparative trial support the improved efficacy rates associated with rFVIIa compared with aPCC.
  
  
  CONCLUSIONS
  The wide variations in definitions of efficacy and study methods make comparison of results across studies difficult. Further head-to-head trials should incorporate a standardized measurement for defining efficacy.
authors.affiliation: RTI Health Solutions, Williams House, Manchester, M15 6SE, UK. cknight@rti.org
authors.forename: Chris
authors.initials: C
authors.lastname: Knight
authors.forename: Anne Møller
authors.initials: AM
authors.lastname: Danø
authors.forename: Tessa
authors.initials: T
authors.lastname: Kennedy-Martin
mesh_terms: D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015201:Meta-Analysis as Topic; D010146:Pain / Q000209:etiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa