Patient data meta-analysis of Post-Authorization Safety Surveillance (PASS) studies of haemophilia A patients treated with rAHF-PFM

Alfonso Iorio, M. Marcucci, J. Cheng, J. Oldenburg, C. Schoenig-Diesing, E. Matovinovic, V. Romanov, L. Thabane

Research output: Contribution to journalArticlepeer-review


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). Primary outcome: de novo inhibitors in severe, previously treated patients (PTPs) with > 150 EDs. Secondary outcomes: de novo inhibitors according to prior exposure and disease severity; other adverse events; annualized bleeding rate (ABR). Analysis: 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.

Original languageEnglish
Pages (from-to)777-783
Number of pages7
Issue number6
Publication statusPublished - Nov 1 2014


  • Bleeding rate
  • Factor VIII
  • Factor VIII inhibitors
  • Hemophilia A
  • Post-marketing
  • Surveillance

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)
  • Medicine(all)


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