For previously untreated patients with severe hemophilia A, the risk of developing factor VIII (FVIII) inhibitors becomes marginal after 75 exposure days, according to an observational study of more than 1,000 infants on prophylaxis.
“Most inhibitors develop during the first 50 exposure days to FVIII, with 50% of inhibitors already present after 14-15 exposure days,” wrote H. Marijke van den Berg, MD, PhD, of the PedNet Haemophilia Research Foundation, Baarn, the Netherlands. The findings were published in Blood.
Dr. van den Berg and her colleagues aimed to characterize the risk of inhibitor development beyond 50 exposure days and to calculate the age when patients reach near-zero risk. The researchers followed 1,038 previously untreated patients with severe hemophilia A from first exposure to FVIII until inhibitor development, up to a maximum of 1,000 exposure days. Data was obtained from the PedNet Haemophilia Registry.
From the initial cohort, 943 patients (91%) were followed until 50 exposure days, and 899 (87%) were followed until 75 exposure days. Inhibitor development was defined by a minimum of two positive inhibitor titers in conjunction with reduced in-vivo FVIII recovery. The team also conducted a survival analysis to measure inhibitor incidence and reported median ages at initial exposure and at exposure day 75.
After analysis, the researchers found that 298 of 300 (99.3%) occurrences of inhibitor development ensued within 75 exposure days. No inhibitor development occurred between exposure day 75 and 150. The final two occurrences developed at exposure day 249 and 262, each with a low titer. The median age at first exposure was 1.1 years versus 2.3 years at exposure day 75.
“Our study shows that children on prophylaxis reach a near-zero risk plateau of inhibitor development at 75 [exposure days] only 1.2 years after the first [exposure day],” they wrote.
The researchers explained that these findings could impact the design of future clinical studies for previously untreated patients with severe hemophilia A. And they noted that these data are applicable to patients administered early prophylaxis, since the majority of study participants began prophylaxis early in life. “Frequent testing for inhibitors until 75 instead of 50 exposure days, therefore, is feasible and should be recommended for all [previously untreated patients],” they concluded.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: van den Berg HM et al. Blood. 2019 Jun 11. doi: 10.1182/blood.2019000658.