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Thromb Haemost 2015; 114(04): 670-675
DOI: 10.1160/TH14-12-1044
Coagulation and Fibrinolysis
Schattauer GmbH

Inhibitor development in non-severe haemophilia across Europe

Kathelijn Fischer
1   Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, The Netherlands
2   Van Creveldkliniek, University Medical Centre Utrecht, The Netherlands
,
Alfonso Iorio
3   Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Toronto, Canada
4   Department of Medicine, McMaster University, Hamilton, Canada
,
Riitta Lassila
5   Department of Hematology, Unit of Coagulation Disorders, Helsinki University Central Hospital, Finland
,
Flora Peyvandi
6   Angelo Bianchi Bonomi, Hemophilia and Thrombosis centre, IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
7   Department of pathophysiology and Transplantation, University of Milan, Milan, Italy
,
Gabriele Calizzani
8   European Haemophilia consortium and Italian National Blood Centre, Rome, Italy
,
Alex Gatt
9   Mater Dei Hospital, Tal-QRoqq, Msida, Malta
,
Thierry Lambert
10   Hopital Bicetre, Paris, France
,
Jerzy Windyga
11   Institute for Hematology and Transfusion Medicine, Warsaw, Poland
,
Estelle A. Gilman
12   Department of Cardiovascular Science, University of Sheffield, Sheffield, UK
,
Michael Makris
12   Department of Cardiovascular Science, University of Sheffield, Sheffield, UK
13   Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK
,
the EUHASS participants › Author Affiliations Financial support: The EUHANET project is funded by the European Commission Health Programme through the Executive Agency for Health and Consumers (EAHC) (Project number 2011207) with co-financing from 12 pharmaceutical manufacturers. The pharma -ceutical companies supporting this project are Baxter, Bayer, Biotest, BPL, CSL Behring, Grifols, Kedrion, LFB, NovoNordisk, Octapharma, Pfizer, SOBI/Biogen Idec.
Further Information

Publication History

Received: 17 December 2014

Accepted after major revision: 23 April 2015

Publication Date:
29 November 2017 (online)

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Summary

Evidence about inhibitor formation in non-severe haemophilia and the potential role for clotting factor concentrate type is scant. It was the aim of this study to report inhibitor development in non-severe haemophilia patients enrolled in the European Haemophilia Safety Surveillance (EUHASS) study. Inhibitors are reported quarterly and total treated patients annually. Incidence rates and 95 % confidence intervals (95 % CI) were calculated according to diagnosis and concentrate used. Between 1–10–2008 and 31–12–2012, 68 centres reported on 7,969 patients with non-severe haemophilia A and 1,863 patients with non-severe haemophilia B. For haemophilia A, 37 inhibitors occurred in 8,622 treatment years, resulting in an inhibitor rate of 0.43/100 treatment years (95 % CI 0.30–0.59). Inhibitors occurred at a median age of 35 years, after a median of 38 exposure days (EDs; P25-P75: 20-80); with 72 % occurring within the first 50 EDs. In haemophilia B, one inhibitor was detected in 2,149 treatment years, resulting in an inhibitor rate of 0.05/100 years (95% CI 0.001–0.26). This inhibitor developed at the age of six years, after six EDs. The rate of inhibitors appeared similar across recombinant and plasma derived factor VIII (FVIII) concentrates. Rates for individual concentrates could not be calculated at this stage due to low number of events. In conclusion, inhibitors in non-severe haemophilia occur three times more frequently than in previously treated patients with severe haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100 years (haemophilia B). Although the majority of inhibitors developed in the first 50 EDs, inhibitor development continued with increasing exposure to FVIII.

Keywords

Factor VIII inhibitors - epidemiological studies - haemophilia A / B - haemophilia therapy - non-severe haemophilia - factor concentrates

* A complete list of EUHASS participants is given in the Suppl. Material (available online at www.thrombosis-online.com).


 

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