Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study

Autor: Christoph Male, Nadine G. Andersson, Anne Rafowicz, Ri Liesner, Karin Kurnik, Kathelijn Fischer, Helen Platokouki, Elena Santagostino, Hervé Chambost, Beatrice Nolan, Christoph Königs, Gili Kenet, Rolf Ljung, Marijke Van den Berg, null PedNet study group
Přispěvatelé: Medizinische Universität Wien = Medical University of Vienna, Skane University Hospital [Malmo], Lund University [Lund], Hôpital Bicêtre, Great Ormond Street Hospital for Children [London] (GOSH), University of Munich Medical Center, Partenaires INRAE, University Medical Center [Utrecht], Sophia Children's Hospital, CHU Milan, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Our Lady's Children's Hospital Crumlin (OLCHC), J.W.Goethe University Hospital, Chaim Sheba Medical Center, PedNet Haemophilia Research Foundation, Lucas, Nelly, Department of Paediatrics, Medical University of Vienna, Vienna
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Haematologica
Haematologica, 2021, 106 (1), pp.123-129. ⟨10.3324/haematol.2019.239160⟩
Haematologica, Ferrata Storti Foundation, 2020, 106 (1), pp.123-129. ⟨10.3324/haematol.2019.239160⟩
ISSN: 0390-6078
1592-8721
Popis: The incidence of factor IX (FIX) inhibitors in severe hemophilia B (SHB) is not well defined. Frequencies of 3-5% have been reported but most studies to date have been small, including patients with different severities, and without prospective follow up for inhibitor incidence. The study objective was to investigate the inhibitor incidence in patients with SHB followed up for to 500 exposure days (ED), the frequency of allergic reactions, and the relationship with genotypes. Consecutive previously untreated patients (PUP) with SHB enrolled into the PedNet cohort were included. Detailed data was collected for the first 50 ED, followed by the annual collection of the inhibitor status and allergic re-actions. The presence of inhibitors was defined by at least two consecutive positive samples. Additionally, data on FIX gene mutation was collected. One hundred and fifty-four PUP with SHB were included; 75% were followed up until 75 ED, and 43% until 500 ED. Inhibitors developed in 14 patients (seven high-titer). The median number of ED at inhibitor manifestation was 11 (interquartile range [IQR]: 6.5-36.5). The cumulative inhibitor incidence was 9.3% (95% Confidence Interval [CI]: 4.4-14.1) at 75 ED, and 10.2% (95% CI: 5.1-15.3) at 500 ED. Allergic reactions occurred in four (28.6%) inhibitor patients. Missense mutations were most frequent (46.8%) overall but not associated with inhibitors. Nonsense mutations and deletions with large structural changes comprised all mutations among inhibitor patients and were associated with an inhibitor risk of 26.9% and 33.3%, respectively. In an unselected, well-defined cohort of PUP with SHB, the cumulative inhibitor incidence was 10.2% at 500 ED. Nonsense mutations and large deletions were strongly associated with the risk of inhibitor development. The ‘PedNet Registry’ is registered at clinicaltrials.gov; identifier: NCT02979119.
Databáze: OpenAIRE
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