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

The timing of prophylaxis and F8 genotype can impact treatment outcomes in adults with severe haemophilia A (HA). To investigate how F8 genotype, timing, and type of prophylaxis influence arthropathy, bleeding rates, factor consumption and health-related quality of life (HRQoL). Thirty-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. The 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. Delayed 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.