Background Treatment of severe Hemophilia A (SHA) with FVIII concentrates is complicated by development of neutralizing inhibitors in about 30% during the first 50 exposure days (EDs). Despite extensive research, inhibitor risk of different FVIII concentrates remains to be elucidated.Aim to analyze inhibitor development according to (classes of) individual FVIII concentrates in previously untreated patients (PUPs) with SHA.Methods PUPs with SHA born between 2000-2024 were followed until inhibitor development or 50 EDs. Inhibitor development according to classes of FVIII concentrates, i.e. plasma derived (pdFVIII) vs recombinant (rFVIII), standard vs extended half-life (SHL-rFVIII vs EHL-rFVIII), and individual concentrates used by ≥40 PUPs were compared using multivariable Cox regression (generating rate ratios (RR) with 95% Confidence Intervals (CI)).Results 1503 PUPs were included. Inhibitors developed in 444 PUPs after a median of 12 EDs (cumulative incidence 31.0% (CI 28.6-33.4%). Compared to SHL-rFVIII, inhibitor risk was similar for pdFVIII (RR 0.89 ; CI 0.69-1.14) and EHL-rFVIII (RR 1.10; CI 0.75-1.61). Nine individual FVIII concentrates (5 SHL-rFVIII, 1 EHL-rFVIII, 3 pdFVIII) were compared to Advate (n=392): only KogenateFS/HelixateNexGen (n=307, RR 1.40; CI 1.07-1.82, p-value 0.013) and Fanhdi (n=50, RR 1.72; CI 1.11-2.68, p-value 0.024) showed increased inhibitor risk.Conclusions Inhibitor development occurred in 31.0% of PUPs, with similar incidence across SHL-rFVIII, EHL-rFVIII, and pdFVIII. Analysis of individual concentrates showed increased inhibitor risk for KogenateFS/HelixateNexGen (SHL-rFVIII) and for the first time for Fanhdi (pdFVIII). In the absence of formal PUP studies, PedNet will continue evaluating inhibitor risk according to individual FVIII concentrates.
Fischer et al. (Mon,) studied this question.