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Thromb Haemost 2015; 113(05): 968-975
DOI: 10.1160/TH14-10-0826
Coagulation and Fibrinolysis
Schattauer GmbH

Inhibitor development in haemophilia according to concentrate

Four-year results from the European HAemophilia Safety Surveillance (EUHASS) project
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
,
Riita Lassila
3   Department of Hematology, Unit of Coagulation Disorders, Helsinki University Central Hospital, Finland
,
Flora Peyvandi
4   Angelo Bianchi Bonomi, Hemophilia and Thrombosis centre, IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
5   Department of pathophysiology and Transplantation, University of Milan, Milan, Italy
,
Gabriele Calizzani
6   European Haemophilia consortium and Italian National Blood Centre, Rome, Italy
,
Alex Gatt
7   Mater Dei Hospital, Tal-QRoqq, Msida, Malta;
,
Thierry Lambert
8   Hopital Bicetre, Paris, France
,
Jerzy Windyga
9   Institute for Hematology and Transfusion Medicine, Warsaw, Poland
,
Alfonso Iorio
10   Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
11   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Estelle Gilman
12   Department of Cardiovascular Science, University of Sheffield, Sheffield, UK;
,
Michael Makris
13   Sheffield Haemophilia and Thrombosis Centre, University of Sheffield, Sheffield, UK
› Author Affiliations
Further Information

Publication History

Received: 02 October 2014

Accepted after major revision: 21 January 2014

Publication Date:
24 November 2017 (online)

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Summary

Inhibitor development represents the most serious side effect of haemophilia treatment. Any difference in risk of inhibitor formation depending on the product used might be of clinical relevance. It was this study’s objective to assess inhibitor development according to clotting factor concentrate in severe haemophilia A and B. The European Haemophilia Safety Surveillance (EUHASS) was set up as a study monitoring adverse events overall and according to concentrate. Since October 2008, inhibitors were reported at least quarterly. Number of treated patients was reported annually, specifying the number of patients completing 50 exposure days (Previously Untreated Patients, PUPs) without inhibitor development. Cumulative incidence, incidence rates and 95 % confidence intervals (CI) were calculated. Data from October 1, 2008 to December 31, 2012 were analysed for 68 centres that validated their data. Inhibitors developed in 108/417 (26 %; CI 22–30 %) PUPs with severe haemophilia A and 5/72 (7 %; CI 2–16%) PUPs with severe haemophilia B. For Previously Treated Patients (PTPs), 26 inhibitors developed in 17,667 treatment years [0.15/100 treatment years; CI 0.10–0.22) for severe haemophilia A and 1/2836 (0.04/100; (CI 0.00–0.20) for severe haemophilia B. Differences between plasma-derived and recombinant concentrates, or among the different recombinant FVIII concentrates were investigated. In conclusion, while confirming the expected rates of inhibitors in PUPs and PTPs, no class or brand related differences were observed.

Keywords

Adverse Drug Reaction Reporting Systems - antibodies - neutralising - factor VIII - haemophilia A - haemophilia B

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


 

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