In a study of patients with hemophilia A (HA) in Thailand, researchers identified improvements in clinical outcomes after patients were switched from a factor VIII (FVIII) concentrate product with a standard half-life (SHL) to a product with an extended half-life (EHL). These and other study findings were recently published in a report in the journal Haemophilia.
Use of EHL FVIII concentrates having a median of 1.3- to 1.6-fold longer half-life, compared with SHL FVIII concentrates, potentially may reduce prophylactic dosing from 3 to 2 times per week, the researchers explained in their report. However, there may be variation among patients in the dose of EHL FVIII concentrate that is needed.
The research team conducted this study to identify outcomes with low-dose FVIII prophylaxis using PK-guided EHL FVIII concentrate dosing after use of SHL FVIII concentrate. The single-center, prospective study (ClinicalTrials.gov Identifier: NCT05281185) included Thai patients with severe HA or moderate HA and a severe bleeding phenotype.
The study enrolled patients who had been using low-dose, weight-based SHL FVIII prophylaxis. PK-based, low-dose EHL FVIII prophylaxis was administered to patients for 6 months. Hemophilia-related outcomes were compared between the periods of SHL, versus EHL, FVIII prophylaxis. Additionally, the investigators assessed consumption of FVIII concentrate products before and after the switch between these prophylactic therapy approaches.
The study included 15 participants who had a mean age of 18.7 years (range, 7-25). The level of FVIII coagulant activity at baseline was below 1 IU/dL in 73.3% of patients. In this study, there appeared to be improvements in clinical outcomes after the switch between prophylaxis regimens.
The median annualized bleeding rates totaled 22 (interquartile range [IQR], 6-28) with SHL FVIII prophylaxis and 10 (IQR, 2-14) with EHL FVIII prophylaxis (P =.001). Median annualized joint bleeding rates were 18 (IQR, 6-24) with SHL FVIII and 2 (IQR, 0-12) with EHL FVIII (P =.001). Additionally, Hemophilia Joint Health Scores (HJHSs) were lower after switching; median scores were 20 (IQR, 4-32) with SHL FVIII and 13 (IQR, 2-28) with EHL FVIII (P =.001) on the HJHS version 2.1 scale.
After switching to the PK-guided EHL FVIII concentrate regimen, patient quality of life scores also showed improvement (P =.001). Adherence rates were similar between regimens, with medians of 90% for SHL FVIII prophylaxis and 88% for EHL FVIII prophylaxis (P =.051).
In an evaluation of FVIII consumption, with SHL FVIII concentrate, the median consumption was 1288.9 FVIII IU/kg/year, and with EHL FVIII concentrate the median consumption was 1724.8 FVIII IU/kg/year. However, the difference did not reach statistical significance (P =.05).
“This prospective study showed the effective and practical regimen of a 6-month low-dose PK-guided EHL FVIII prophylaxis in severe or moderate HA patients in Thailand,” the researchers wrote in their report.” They concluded that the regimen was associated with improvements in bleeding rates, joint health scores, and quality of life, even with a tendency toward higher FVIII consumption using this regimen.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Rakmanotham A, Moonla C, Sosothikul D. Clinical outcomes of low-dose pharmacokinetic-guided extended half-life versus low-dose standard half-life factor VIII concentrate prophylaxis in haemophilia A patients. Haemophilia. Published online November 21, 2022. doi:10.1111/hae.14700