The incidence of inhibitors in previously untreated patients with severe hemophilia B was found to be 10.2% at a time point of 500 exposure days, according to a recent study (ClinicalTrials.gov Identifier: NCT02979119) based on data from the PedNet Registry. The study results were published in Haematologica.

According to the study investigators, past research has suggested the incidence of inhibitors is lower for patients with hemophilia B (1%-5%) compared with patients with hemophilia A (25%-35%), but they explained that detailed studies on inhibitor incidence in patients with hemophilia B have been limited by the relatively low prevalence of this condition.

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In this prospective study, a birth cohort of patients with hemophilia A or B was monitored for baseline characteristics, treatment, and outcomes. Genetic analyses were performed on patient samples to identify the presence of mutations. Incidence of clinically relevant inhibitors in patients with severe hemophilia B was the primary focus of this report.

From the cohort of 154 previously untreated patients with severe hemophilia B, 43% of patients were still being followed by 500 exposure days. The inhibitor incidence in these patients at 500 exposure days was 10.2% (95% CI, 5.1%-15.3%). Half of the 14 patients with inhibitors had high inhibitor titers, and 28.6% of patients with inhibitor development experienced allergic reactions. Inhibitors appeared at a median of 11 exposure days (interquartile range, 6.5-36.5).

Patients with inhibitors had factor IX inhibitors present in their family histories more often than patients without inhibitors (21% vs 2%).

Analyses of mutations showed that 46.8% of patients had missense mutations, but these did not show relationships with inhibitor development. However, patients who developed inhibitors showed a rate of 26.9% for nonsense mutations. Deletions associated with substantial structural changes were found in 33.3% of patients who had inhibitors.

The investigators reported that the inhibitor incidence found in this study was higher than that found in some prior studies, and they concluded that deletions and nonsense mutations were possible risk factors for inhibitors.

Reference

1.     Male C, Andersson NG, Rafowicz A, et al; and PedNet study group. Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study [published online January 9, 2020]. Haematologica. doi:10.3324/haematol.2019.239160