Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe haemophilia A, 2000-2011

Peter W. Collins, Benedict P. Palmer, Elizabeth A. Chalmers, Daniel P. Hart, Ri Liesner, Savita Rangarajan, Katherine Talks, Michael Williams and Charles R.M. Hay

Key points

  • Kogenate Bayer/Helixate Nexgen was associated with a higher inhibitor incidence than Advate in 407 consecutive UK severe hemophilia A PUPs.

  • Other risk factors for inhibitor development were factor VIII genotype, ethnicity and intensive treatment episodes.


The effect of recombinant factor VIII (rFVIII) brand on inhibitor development was investigated in all 407 severe haemophilia A previously untreated patients born in the UK between 1/January/2000 and 31/December/2011. Eighty-eight (22%) had been in the RODIN study. Information was extracted from the National Haemophilia Database. Since exposure days (EDs) were not known for some patients, time from first treatment was used as a surrogate for rFVIII exposure. An inhibitor developed in 118 (29%) patients, 60 high and 58 low titre, after a median (interquartile range) 7.8 (3.3-13.5) months from first exposure and 16 (9-30) EDs. Of 128 patients treated with Kogenate Bayer/Helixate Nexgen 45 (35.2%, 95% CI 27.4-43.8) developed an inhibitor compared with 42/172 (24.4%, 95%CI 18.6-31.4%) with Advate (P=0.04). The adjusted hazard ratio (95% CI) for Kogenate Bayer/Helixate Nexgen compared to Advate was 2.14 (1.12-4.10), P=0.02 for high titre and 1.75 (1.11-2.76), P=0.02 for all inhibitors. When excluding UK-RODIN patients the adjusted HR (95% CI) for high titre inhibitors was 2.00 (0.93-4.34), P=0.08. ReFacto AF was associated with a higher incidence of all, but not high titre, inhibitors than Advate. These results will help inform debate around the relative immunogenicity and use of rFVIII brands.

  • Submitted July 17, 2014.
  • Accepted October 14, 2014.