PB1119 - The impact of recombinant factor Ⅷ products on inhibitor development in previously untreated and previously treated children with hemophilia A: a systematic review

Background: Currently, the comparative data on inhibitor development of recombinant factor Ⅷ (rFⅧ) products in pediatric hemophilia A (HA) patients is lacked.

Aims: This systematic review evaluated the inhibitor development of available third-generation standard half-life (SHL) and extended half-life (EHL) rFⅧ products in pediatric HA patients, previously treated (PTPs) or untreated (PUPs).

Methods: Following PRISMA guidelines, we conducted a systematic search of clinical studies from PubMed, Embase, and Cochrane Library. The studies included HA patients aged ≤12 years receiving rFⅧ treatment. Inhibitor development rates was extracted and performed with a single-arm meta-analysis.

Results: Nine studies involving 741 HA patients were identified, including one randomized non-controlled study and eight observational studies. In PUPs, patients treated with EHL rFⅧ had a lower inhibitor development rate compared to third-generation SHL rFⅧ [0.29 (95% CI: 0.23; 0.35) vs 0.37 (95% CI: 0.28; 0.48)]. Among the third-generation SHL rFⅧ products, the inhibitor development rates in full-length rFⅧ products was 0.36 (95% CI: 0.22; 0.58). Jonker CS et al. reported the lowest inhibitor development rate of 0.27 (95% CI: 0.20; 0.35). The high-titer inhibitor development rates in third-generation SHL rFⅧ was 0.21 (95% CI: 0.14; 0.32) and in full-length third-generation rFⅧ was 0.21 (95% CI: 0.11; 0.41). Auerswald G et al. reported the lowest high-titer inhibitor development rate of 0.13 (95% CI: 0.05; 0.24) (Table 1 and Figure 1).

Conclusion(s): In HA pediatric patients, the inhibitor development may be associated with the type of rFⅧ product used, and it need to be closely monitored during rFⅧ treatment.