title: Patient data meta-analysis of Post-Authorization Safety Surveillance (PASS) studies of haemophilia A patients treated with rAHF-PFM.
abstract: A Post-Authorization Safety Study (PASS) global program was designed to assess safety and effectiveness of rAHF-PFM (ADVATE) use in haemophilia patients in routine clinical settings. The main aim of this project was to estimate the rate of inhibitors and other adverse events across ADVATE-PASS studies by meta-analysing individual patient data (IPD). Eligible Studies: PASS studies conducted in different countries, between 2003 and 2013, for which IPD were provided. Eligible patients: haemophilia A patients with baseline FVIII:C < 5%, with a known number of prior exposure days (EDs).
  
  
  METHODS
  de novo inhibitors in severe, previously treated patients (PTPs) with > 150 EDs.
  
  
  RESULTS
  de novo inhibitors according to prior exposure and disease severity; other adverse events; annualized bleeding rate (ABR).
  
  
  METHODS
  random-effects logistic regression. Five of seven registered ADVATE-PASS (Australia, Europe, Japan, Italy and USA) and 1188 patients were included (median follow-up 384 days). Among severe PTPs with > 150 EDs, 1/669 developed de novo inhibitors (1.5 per 1000; 95% confidence interval [CI] 0.2, 10.6 per 1000). Among all patients included in the PASS studies, 21 developed any type of inhibitors (2.0%, 95% CI: 0.8%, 4.7%). Less than 1% of patients presented with other serious adverse events possibly related to ADVATE. The overall median ABR was 3.83 bleeds/year (first, third quartiles: 0.60, 12.90); 1.66 (0, 4.78) in the 557 patients continuously on prophylaxis ≥ twice/week. Meta-analysing PASS data from different countries confirmed the overall favourable safety and effectiveness profile of ADVATE in routine clinical settings.
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Iorio
authors.forename: M
authors.initials: M
authors.lastname: Marcucci
authors.forename: J
authors.initials: J
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.forename: C
authors.initials: C
authors.lastname: Schoenig-Diesing
authors.forename: E
authors.initials: E
authors.lastname: Matovinovic
authors.forename: V
authors.initials: V
authors.lastname: Romanov
authors.forename: L
authors.initials: L
authors.lastname: Thabane
mesh_terms: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006467:Hemophilia A / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D011358:Product Surveillance, Postmarketing; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D011994:Recombinant Proteins; D005169:Factor VIII
keywords: bleeding rate; factor VIII; factor VIII inhibitors; hemophilia A; post-marketing; surveillance