PRAGUE—For previously untreated patients (PUPs) with severe hemophilia A, the risk of developing factor VIII (FVIII) alloantibodies (inhibitors) becomes negligible after 75 exposure days, according to a recent study involving more than 1,000 infants.
Will Pass/ MDedge News
Dr. H. Marijke van den Berg
This finding answers a long-standing and important question in the management of hemophilia A, reported lead author H. Marijke van den Berg, MD, PhD, of University Medical Centre in Utrecht, The Netherlands.
Inhibitor development is the biggest safety concern facing infants with severe hemophilia A because it affects 25%-35% of the patient population, but no previous studies have adequately described the associated risk profile, she noted.
“Most studies until now collected data until about 50 [exposure days] and not that far beyond,” Dr. van den Berg said at the annual congress of the European Association for Haemophilia and Allied Disorders. “So we were interested to see the serum plateau in our large cohort.”
Such a plateau would represent the time point at which risk of inhibitor development approaches zero.
Dr. van den Berg and her colleagues followed 1,038 PUPs with severe hemophilia A from first exposure to FVIII onward. Data were from drawn from the PedNet Registry. From the initial group, 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 addition to determining the point in time of inhibitor development, the investigators performed a survival analysis for inhibitor incidence and reported median ages at first exposure and at exposure day 75.
The results showed that 298 out of 300 instances of inhibitor development occurred within 75 exposure days, and no inhibitors developed between exposure day 75 and 150. The final two instances occurred at exposure day 249 and 262, both with a low titer.
Median age at first exposure was 1.1 years, compared with 2.3 years at exposure day 75.
These findings suggest that risk of inhibitors is “near zero” after 75 days and that risk is approaching zero just 1 year after first exposure to FVIII, she said.
The results from this study could affect the design of future clinical trials for PUPs.
“Our recommendation will be to continue frequent [inhibitor] testing until 75 exposure days,” Dr. van den Berg said.
The time frame involved is very short, so close monitoring should be feasible for investigators, she noted.
Dr. van den Berg said that additional data, including Kaplan-Meier curves, would “hopefully” be published in a journal soon.
Dr. van den Berg reported having no relevant financial disclosures.
SOURCE: van den Berg HM et al. EAHAD 2019, Abstract OR05.