Different inhibitor incidence for individual factor VIII concentrates in 1076 previously untreated patients with severe hemophilia A: data from the PedNet cohort.

Development of inhibitory antibodies (inhibitors) against infused factor VIII (FVIII) remains the major side effect of treatment of severe hemophilia A (SHA), which develops in ±30% of patients, mostly during the first 50 exposure days (EDs) to clotting factor concentrates [ 1 Gouw S.C. Van Der Bom J.G. Ljung R. Escuriola C. Cid A.R. Claeyssens-Donadel S. Van Geet C. Kenet G. Mäkipernaa A. Molinari A.C. Muntean W. Kobelt R. Rivard G. Santagostino E. Thomas A. Van Den Berg H.M. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med. 2013; 368: 231-239 Crossref PubMed Scopus (351) Google Scholar , 2 Volkers P. Hanschmann K.M. Calvez T. Chambost H. Collins P.W. Demiguel V. Hart D.P. Hay C.R.M. Goudemand J. Ljung R. Palmer B.P. Santagostino E. van Hardeveld E.M. van den Berg M. Keller-Stanislawski B. Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: combined analysis of three studies. Haemophilia. 2019; 25: 398-407 Crossref PubMed Scopus (19) Google Scholar ]. Many genetic (nonmodifiable) and nongenetic (potentially modifiable) risk factors for inhibitor development have been identified. Among these, the inhibitor risk associated with the class of FVIII concentrates (plasma-derived [pdFVIII] vs recombinant [rFVIII]) and with specific FVIII concentrates are controversial, especially as studies have suffered from limited numbers, reducing statistical precision. The RODIN study, reporting on 574 previously untreated patients (PUPs) from the PedNet Registry, suggested an increased inhibitor incidence in PUPs using Kogenate FS/Helixate NexGen (Kogenate) compared with Advate [ 1 Gouw S.C. Van Der Bom J.G. Ljung R. Escuriola C. Cid A.R. Claeyssens-Donadel S. Van Geet C. Kenet G. Mäkipernaa A. Molinari A.C. Muntean W. Kobelt R. Rivard G. Santagostino E. Thomas A. Van Den Berg H.M. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med. 2013; 368: 231-239 Crossref PubMed Scopus (351) Google Scholar ]. This finding has been corroborated by pooled individual studies [ 2 Volkers P. Hanschmann K.M. Calvez T. Chambost H. Collins P.W. Demiguel V. Hart D.P. Hay C.R.M. Goudemand J. Ljung R. Palmer B.P. Santagostino E. van Hardeveld E.M. van den Berg M. Keller-Stanislawski B. Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: combined analysis of three studies. Haemophilia. 2019; 25: 398-407 Crossref PubMed Scopus (19) Google Scholar ] and a meta-analysis [ 3 Rota M. Cortesi P.A. Steinitz-Trost K.N. Reininger A.J. Gringeri A. Mantovani L.G. Meta-Analysis on incidence of inhibitors in patients with haemophilia A treated with recombinant factor VIII products. Blood Coagul Fibrinolysis. 2017; 28: 627-637 Crossref PubMed Scopus (19) Google Scholar ]. However, detailed analyses of individual patient data with adjustments for other risk factors are lacking. We analyzed inhibitor incidence according to classes of concentrates as well as for individual FVIII concentrates in the extended PedNet cohort.