Incidence of inhibitors in a cohort of 838 males with hemophilia A previously treated with factor VIII concentrates.

Background: Development of an inhibitory antibody to factor VIII is currently the most serious complication of hemophilia A treatment. The rate of inhibitor development in those that have been previously treated with factor concentrates is poorly defined. Understanding the baseline rate of inhibitor development in the population of previously treated patients (PTPs) is important when evaluating the effect of exposure to new factor replacement products on inhibitor formation.

Objectives: To determine the rate of inhibitor development in PTPs with hemophilia A.

Methods: A cohort of males with hemophilia A who had data collected on four or more occasions prior to 30 March 2003, as part of the Center for Disease Control and Prevention's Universal Data Collection Project, were eligible for inclusion in the cohort. Patients were included in the cohort if they had at least two Bethesda assay measurements and did not have an inhibitor prior to or at the start of the study period. The overall incidence rate was estimated as the number of verified incident inhibitor cases divided by the total follow-up time in years multiplied by 1000 (cases per 1000 person-years).

Results: A total of 838 patients were included in the study. The overall incidence rate was calculated to be 2.14 cases per 1000 person years. All incident cases had more than 50 exposure days prior to inhibitor development.

Conclusions: Given the low rate of inhibitor development in PTPs with hemophilia A, small, non-randomized studies are inadequate to determine the rate of inhibitor development after exposure to novel products. Ongoing, standardized, postmarketing surveillance is needed to determine if novel factor products pose an increased risk of inhibitor development.