Clinical outcomes of low-dose pharmacokinetic-guided extended half-life versus low-dose standard half-life factor VIII concentrate prophylaxis in haemophilia A patients.

Abstract

Despite receiving standard half-life (SHL) factor VIII (FVIII) concentrates prophylaxis, some severe haemophiliaA (HA) patients still encounter spontaneous breakthrough bleeding. Individualized pharmacokinetic (PK)-guided dosing of extended half-life (EHL) FVIII concentrates may reduce their bleeding events. To compare clinical outcomes before and after switching low-dose prophylaxis using weight-based SHL FVIII to PK-guided EHL FVIII concentrates, taking into consideration of a trough FVIII activity at 1IU/dl above natural baseline. In this single-centre prospective cohort, Thai severe or moderate HA (FVIII activity ≤3IU/dl) patients receiving low-dose weight-based SHL FVIII prophylaxis were enrolled. After a 3-day wash-out period, participants underwent low-dose EHL FVIII prophylaxis with PK-based adjustment (myPKFiT® ) for 6 months. The annualized bleeding rates (ABR), the annualized joint bleeding rates (AJBR), the haemophilia-specific quality-of-life (Haemo-QoL or Haemo-QoL-A) scores, the Hemophilia Joint Health Scores (HJHS) and the annualized FVIII consumption were compared between the two prophylactic periods. Of 15 eligible subjects (mean age 18.7±6.7 years), ABR, AJBR and HJHS were significantly reduced (mean differences of -11.1±4.9 bleeds/year, -10.4±5.2 joint bleeds/year and -5.1±1.5 marks, respectively; P<.001 for all comparisons) after switching regimen. The quality-of-life scores had also improved (P=.001). Nonetheless, FVIII consumption tended to increase despite no statistical significance (means of 1240.9±531.3 SHL FVIII IU/kg/year versus 1591.7±438.9 EHL FVIII IU/kg/year; P=.05). This is the first low-dose, PK-guided, EHL FVIII prophylaxis clinical study in Thailand. Benefits and practicability of this personalized regimen may support the implementation of regular FVIII prophylaxis in developing countries with budget constraints. gov NCT05281185.