Background The incidence of factor IX inhibitor development in congenital haemophilia B is low (3–5% depending on the population) and usually occurs in the first days of treatment. Guidelines suggest that, after 150 days exposed to the drug (ED), testing is only required if clinically indicated. But we detected two cases in which the inhibitors developed on long term treatments.
Purpose To describe all worldwide reported cases in which patients developed inhibitors when they were treated with Nonacog alfa. We focused on the time it took to develop the inhibitors since the treatment started.
Material and methods We searched on VigiBase and FEDRA (global and Spanish pharmacovigilance databases, respectively), including all spontaneous reports in patients with Nonacog alfa who developed inhibitors in the past 20 years. All patients who did not have laboratory confirmation were excluded. Age, gender, reporting country, Nonacog alfa treatment starting date, EDs and confirmation inhibitor testing date were recorded.
Results 52 cases of inhibitor development were reported globally: 29 in the USA, 8 in Japan and 15 in Europe. They were primarily in men (45/52) and gender was unknown in 5 cases. Their ages ranged from 9 months to 50 years (age was unknown in 19 cases). It was not possible to confirm the EDs in any of the cases. Half of the notifications (26/52) did not correctly record the chronology of inhibitor development. Of the remainder, 19 notifications were made in the first year of treatment (12 in the first 100 days), 2 notifications between the first and second year, 1 notification between the second and third year, 1 notification between the third and fourth year, 2 notifications between the fourth and fifth year and 1 notification between the sixth and seventh year.
Conclusion These results show that patients treated for several years are also susceptible, although to a lesser extent, to developing inhibitors. Despite the major limitations of this study, it is not wrong to think that patients with longer treatments have been exposed to more doses which might even exceed 150 ED. Hence it is important to monitor all haemophilia B patients throughout all of their treatment.
No conflict of interest
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