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Inhibitor development in previously untreated patients with severe haemophilia A : a nationwide multicentre study in Finland

Vepsäläinen, K. ; Lassila, R. ; Arola, M. ; Huttunen, P. ; Koskinen, S. ; Ljung, R. LU orcid ; Lähteenmäki, P. ; Möttönen, M. and Riikonen, P. (2016) In Haemophilia 22(5). p.721-729
Abstract

Introduction: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. Aim: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL−1). Methods: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. Results: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median... (More)

Introduction: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. Aim: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL−1). Methods: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. Results: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2–13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. Conclusion: The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Haemophilia A, inhibitor, primary prophylaxis, PUP, risk factors, treatment
in
Haemophilia
volume
22
issue
5
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:84990186734
  • pmid:27339837
  • wos:000387390000044
ISSN
1351-8216
DOI
10.1111/hae.12974
language
English
LU publication?
yes
id
0a046efe-7b62-4ce7-bbce-de81dfc7ac41
date added to LUP
2016-11-08 16:14:34
date last changed
2024-10-05 05:17:45
@article{0a046efe-7b62-4ce7-bbce-de81dfc7ac41,
  abstract     = {{<p>Introduction: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. Aim: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C &lt; 0.01 IU mL<sup>−1</sup>). Methods: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. Results: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2–13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. Conclusion: The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.</p>}},
  author       = {{Vepsäläinen, K. and Lassila, R. and Arola, M. and Huttunen, P. and Koskinen, S. and Ljung, R. and Lähteenmäki, P. and Möttönen, M. and Riikonen, P.}},
  issn         = {{1351-8216}},
  keywords     = {{Haemophilia A; inhibitor; primary prophylaxis; PUP; risk factors; treatment}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{5}},
  pages        = {{721--729}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Haemophilia}},
  title        = {{Inhibitor development in previously untreated patients with severe haemophilia A : a nationwide multicentre study in Finland}},
  url          = {{http://dx.doi.org/10.1111/hae.12974}},
  doi          = {{10.1111/hae.12974}},
  volume       = {{22}},
  year         = {{2016}},
}