Efficacy, Effectiveness, and Safety of Prophylaxis With Extended Half-life Factor Viii in People With Hemophilia A: a Systematic Review and Meta-analysis
Year: 2026
Type: article
Study designs: Systematic Review, Meta-Analysis
Abstract: Hemophilia A (HA) is a rare X-linked recessive bleeding disorder caused by mutations in the clotting factor VIII (FVIII) gene. FVIII replacement as prophylaxis prevents bleeding, mainly hemarthroses that may progress into arthropathy, chronic pain, immobility syndrome, and impaired health-related quality of life (HRQoL). Most current available recombinant FVIII (rFVIII) concentrates are divided into standard half-life (SHL)-rFVIII, which requires frequent infusions due to its half-life of ∼12h, whereas extended half-life (EHL)-rFVIII, defined as having a half-life ratio ≥1.3 or an area under the curve ratio >1.25 relative to SHL-rFVIII, enables longer dosing intervals concomitant to higher protective trough levels. We aimed to evaluate the efficacy, effectiveness, and safety of EHL-rFVIII prophylaxis compared with SHL-rFVIII or another EHL-rFVIII in people with HA (PwHA) through a systematic review and meta-analysis. A strategic search was performed in June 2023 for studies comparing prophylaxis with EHL-rFVIII vs. SHL-rFVIII/another EHL-rFVIII. Studies involving >15% PwHA on prophylaxis with plasma-derived FVIII or evaluating overlapping populations were excluded. We included interventional or observational studies. Risk of bias was adapted from the Joanna Briggs Institute tools. Outcomes included bleeding variables, FVIII consumption, adherence, HRQoL, and adverse events. Meta-analyses were performed accordingly. An update of the current analysis is planned for August 2026, and the final data will be shown at HEMO 2026. (CRD42023394281) Of 6,719 records retrieved, we included 26 publications (very low or low risk of bias): 21 (19) cohorts, 1 (1) cross-sectional, and 4 (4) quasi-experimental. The publications were published between 2012 and 2023 and involved 2,632 PwHA (all of whom previously treated). Total (SMD [standard mean differences] -0.68 [95%CI -1.30 to -0.05]; p = 0.03; I2 = 94%; 12 publications evaluating 639 vs. 1,240 PwHA, respectively) and joint annualized bleeding rate was lower with EHL-rFVIII prophylaxis vs. SHL-rFVIII prophylaxis (SMD -0.41 [95%CI -0.59 to -0.23]; p < 0.001; I2 = 0%; 7 publications evaluating 239 vs. 239 PwHA, respectively), while annualized spontaneous bleeding rate was similar (SMD -0.15 [95%CI -0.32 to 0.01]; p = 0,07; I2 = 0%; 3 publications evaluating 199 vs. 497 PwHA, respectively). PwHA with zero total bleed (RR [risk ratio] 1.47 [95%CI 1.13 to 1.90]; p < 0.01; I2 = 63%; 10 publications evaluating 612 vs. 1,185 PwHA, respectively) and zero joint bleed was higher in EHL-rFVIII than SHL-rFVIII prophylaxis (RR 1.48 [95%CI 1.05 to 2.10]; p = 0.03; I2 = 57%; 5 publications evaluating 195 vs. 273 PwHA, respectively). Weekly FVIII consumption did not differ between rFVIII concentrate prophylaxis (SMD -0.05 [95%CI -0.76 to 0.67]; p = 0.90; I2 = 95%; 12 publications evaluating 673 vs. 1274 PwHA, respectively), while treatment adherence was better with EHL-rFVIII than SHL-rFVIII prophylaxis (RR 1.14 [95%CI 1.03 to 1.26]; p = 0.01; I2 = 0%; 4 publications evaluating 243 vs. 297 PwHA, respectively). HRQoL (6 publications) was not meta-analyzed due to heterogeneous assessment. Adverse events (9 publications) were mostly mild with no severe intervention-related events, including inhibitor development. In the current analysis, EHL-rFVIII prophylaxis demonstrated superior clinical effects over SHL-rFVIII prophylaxis in PwHA.
Institution: Universidade Federal de Minas Gerais
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223132125