Moderate- to vigorous-intensity physical activities for hemophilia A patients during low-dose pharmacokinetic-guided extended half-life factor VIII prophylaxis.

BACKGROUND: Low-dose pharmacokinetic (PK)-guided extended half-life (EHL) factor VIII (FVIII) prophylaxis can reduce the bleeding risk in hemophilia A (HA) patients. An increase in physical activities for promoting musculoskeletal health may enhance the benefits of prophylactic therapy. OBJECTIVES: To determine the clinical impact of moderate- to vigorous-intensity physical activities in HA patients during low-dose PK-guided EHL FVIII prophylaxis. PATIENTS/METHODS: This prospective study enrolled patients with moderate/severe HA (baseline FVIII levels ≤ 5 IU/dL) who had received low-dose PK-guided EHL FVIII prophylaxis for ≥ 6 months. An individualized exercise protocol was introduced to each participant, targeting a 65% increase in the maximum predicted heart rate for ≥ 150 min/week, while continuing low-dose PK-guided EHL FVIII prophylaxis for 6 months. Before and after implementing the intervention, annualized bleeding rates (ABR), annualized joint bleeding rates (AJBR), Hemophilia Joint Health Scores (HJHS), skeletal muscle mass, hemophilia-specific quality-of-life (QoL) scores and annualized FVIII consumption were compared. RESULTS: Of 13 participants (mean age ± standard deviation [SD]: 20.1 ± 6.8 years), ABR, AJBR, and HJHS were significantly reduced (mean differences [MD] ± SD: -5.7 ± 2.6 bleeds/year, -4.2 ± 2.6 joint bleeds/year, and -4.3 ± 3.2 marks, respectively; P < 0.05) after applying the 6-month exercise protocol. Skeletal muscle mass and QoL scores had also improved (P = 0.001), while FVIII usage had decreased (MD ± SD: -129.1 ± 208.7 IU/kg/year; P < 0.05). CONCLUSIONS: The combination of moderate- to vigorous-intensity physical activities with low-dose PK-guided EHL FVIII prophylaxis improves bleeding prevention, musculoskeletal status and QoL in patients with moderate/severe HA. By minimizing FVIII consumption, this strategy helps optimize hemophilia care in countries with budget constraints. CLINICALTRIALS: gov NCT05728528.

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

INTRODUCTION: Despite receiving standard half-life (SHL) factor VIII (FVIII) concentrates prophylaxis, some severe haemophilia A (HA) patients still encounter spontaneous breakthrough bleeding. Individualized pharmacokinetic (PK)-guided dosing of extended half-life (EHL) FVIII concentrates may reduce their bleeding events. AIM: 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 1 IU/dl above natural baseline. METHODS: In this single-centre prospective cohort, Thai severe or moderate HA (FVIII activity ≤3 IU/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. RESULTS: 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). CONCLUSIONS: 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. CLINICALTRIALS: gov NCT05281185.