Impact of timing of prophylaxis commencement, F8 genotype and age on factor consumption and health‐related quality of life in patients with severe haemophilia A

Abstract

AbstractIntroductionThe timing of prophylaxis and F8 genotype can impact treatment outcomes in adults with severe haemophilia A (HA).AimTo investigate how F8 genotype, timing, and type of prophylaxis influence arthropathy, bleeding rates, factor consumption and health‐related quality of life (HRQoL).MethodsThirty‐eight patients with severe HA were enrolled. Bleeding events were recorded retrospectively during median 12.5 months. F8 gene variants were classified as null or non‐null. Joint health and HRQoL were assessed with HJHS and EQ‐5D‐5L, respectively.ResultsThe median age at prophylaxis start was 1.25 years in the primary prophylaxis group (N = 15, median age 26 years) and 31.5 years in the secondary group (N = 22, 45 years), respectively. There were significant differences in the medians of HJHS (4 vs. 20, p < .001), EQ‐5D‐5L index (0.9647 vs. 0.904, p = .022), EQ VAS (87 vs. 75, p = .01) and FVIII consumption (3883 vs. 2737 IU/kg/year, p = .02), between the primary and secondary groups, respectively. Median annualized bleeding rate (ABR) was 0 for both groups. Twenty‐five null and thirteen non‐null F8 gene variants were identified. In the secondary prophylaxis group, lower median FVIII consumption (1926 vs. 3370 IU/kg/year) was shown for non‐null compared to null variants, respectively, with similar ABR and HJHS.ConclusionDelayed prophylaxis start with intermediate dose intensity prevents bleeds but at a cost of more arthropathy and reduced HRQoL, compared to higher intensity primary prophylaxis. Non‐null F8 genotype may allow lower factor consumption with similar HJHS and bleeding rates, compared to null genotype.