June 15, 2019

Recombinant factor VIII products are NOT the same

Three European observational studies – from PedNet, FranceCoag Network and UKHCDO – have suggested that second generation recombinant factor VIII products are associated with a high risk of inhibitor development than third-generation alternatives in previously untreated patients with severe haemophilia A. There was some overlap in the patients included in these studies so a new combined analysis of the three databases aims to provide a definitive answer (Haemophilia 2019 May 7. doi: 10.1111/hae.13747).

The main analysis was carried out in a subgroup of 787 patients treated between 2004 and 2013. Of these, 30% developed an inhibitor, which was high-titre in 17%. These figures were similar to the findings from the complete population of 1,109 people treated since 1993. The frequencies of high and any inhibitors was 22% and 37% with the second generation agent and 15% and 26% with the third generation agent.

Compared with a second generation agent (Kogenate), the risk of developing a high titre inhibitor was 28% lower with one third generation agent (Advate), though the 95% confidence intervals included unity, indicating that the possibility of ‘no difference’ could not be excluded (hazard ratio [HR] 0.72, CI95% 0.49 – 1.06). However, the risk of any inhibitor was significantly lower (HR 0.71, CI95% 0.53 – 0.95). There was a similar trend for other third generation agents.

The authors conclude that recombinant factor VIII products have important differences in their risk of inhibitors and they should not be considered identical.