title: Recombinant factor VIIa concentrate versus plasma-derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors.
abstract: BACKGROUND
  In people with haemophilia, therapeutic clotting agents might be recognised as a foreign protein and induce anti-factor VIII antibodies, known as 'inhibitors'. Drugs insensitive to such antibodies, either recombinant or plasma-derived, are called factor VIII 'by-passing' agents and used for treatment of bleeding in people with inhibitors.
  
  
  OBJECTIVE
  To determine the clinical effectiveness of recombinant factor VIIa concentrate compared to plasma-derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors.
  
  
  METHODS
  We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Coagulopathies Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Coagulopathies Trials Register: 23 September 2015.
  
  
  METHODS
  Randomised and quasi-randomised controlled clinical trials comparing recombinant factor VIIa concentrate to human plasma-derived concentrates (high-dose human or recombinant factor VIII or factor IX concentrate; non-activated prothrombin complex concentrates; activated prothrombin complex concentrates) in people with haemophilia. Comparisons with animal-derived products were excluded.
  
  
  METHODS
  Two authors independently assessed the trials (eligibility and risk of bias) and extracted data. No combined meta-analyses were performed due to the unavailability of outcomes and comparisons common to the included trials.
  
  
  RESULTS
  A total of 15 trials were identified, two of which (with data for a total of 69 participants) were eligible for analysis. Both trials showed methodological flaws and did not show superiority of one treatment over the other. Both the treatments showed that recombinant factor VIIa and activated prothrombin complex concentrate appeared to have a similar haemostatic effect in both trials, without increasing thromboembolic risk.
  
  
  CONCLUSIONS
  Based on the separate analysis of the two available randomised trials, recombinant factor VIIa and activated prothrombin complex concentrate were found to be similar in efficacy and safety. However, there is a need for further, well-designed, adequately-powered, randomised controlled trials to assess the relative benefits and risks of using recombinant factor VIIa compared to human plasma-derived concentrates in people with haemophilia with inhibitors. It is advisable that researchers in the field define commonly agreed objective outcome measures in order to enable the pooling of their results, thus increasing the power of comparisons. To date, data could not be combined in a formal meta-analysis. For the same reason reporting concordant and discordant pairs in cross-over trials is recommended.
authors.affiliation: Department of Internal Medicine, University of Perugia, Ospedale Santa Maria della Misericordia, Località Sant'Andrea delle Fratte, Perugia, Italy, 06126.
authors.forename: Davide
authors.initials: D
authors.lastname: Matino
authors.forename: Michael
authors.initials: M
authors.lastname: Makris
authors.forename: Kerry
authors.initials: K
authors.lastname: Dwan
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Amico
authors.forename: Alfonso
authors.initials: A
authors.lastname: Iorio
mesh_terms: D000208:Acute Disease; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D005169:Factor VIII / Q000276:immunology / Q000627:therapeutic use; D015942:Factor VIIa / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII; C103587:recombinant FVIIa; C065655:anti-inhibitor coagulant complex; D015942:Factor VIIa