PB0689 - Efficacy/effectiveness of extended half-life factor VIII concentrates on the prophylaxis of people with hemophilia A: A systematic review and meta-analysis

Background: The treatment of people with hemophilia A (PwHA) consists of infusing clotting factor VIII (FVIII), either as prophylaxis (to prevent bleeding) or on-demand (to stop a bleeding episode). The infusion frequency of prophylactic standard half-life (SHL)-FVIII concentrates can be burdensome for PwHA. Extended half-life (EHL)-FVIII concentrates were developed to facilitate the prophylaxis regimen by increasing the time between infusions, but higher trough levels of FVIII may be reached with more frequent administration.

Aims: We aimed to evaluate the efficacy/effectiveness of EHL-FVIII concentrates compared with SHL-FVIII concentrates as prophylaxis of PwHA.

Methods: The study followed the PRISMA2020 statement. The search strategies (01/10/2022) were structured according to literature databases. Clinical trials and observational studies that evaluated prophylaxis with EHL-FVIII compared with SHL-FVIII were included. Two independent reviewers selected publications and extracted data using a standardized form. The bleeding rate outcomes (both annual or annualized) and the total consumed dose of FVIII (weekly) were analyzed. [PROSPERO CRD42021281642]

Results: Twenty-three publications evaluated alfarurioctocog-pegol, alfaefmoroctocog, and alfalonoctocog. Overall bleeding outcomes were lower for PwHA on EHL-FVIII than on SHL-FVIII prophylaxes: total bleeding rate (587 EHL-FVIII vs. 941 SHL-FVIII; standardized mean difference [SMD] -0.43, 95%CI -0.77 to -0.08; I2=87%; p=0.01), spontaneous bleeding rate (127 EHL-FVIII vs. 178 SHL-FVIII; SMD -0.29, 95%CI -0.52 to 0.06; I2=0%; p=0.01), and joint bleeding rate (139 EHL-FVIII vs. 139 SHL-FVIII; SMD -0.31 95%CI -0.55 to -0.07; I2=0%; p=0.01). However, the total consumed doses of FVIII were similar for EHL-FVIII and SHL-FVIII prophylaxes (504 EHL-FVIII vs. 867 SHL-FVIII; SMD -0.13, 95%CI -0.67 to 0.40; I2=95%; p=0.62). The methodological quality of the included publications was moderate in most studies. The certainty of the evidence was low for the total bleeding rate and very low for the total consumed dose of FVIII.

Conclusion(s): EHL-FVIII prophylaxis has better efficacy/effectiveness than SHL-FVIII prophylaxis for PwHA, with a similar consumption.