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Increased inhibitor incidence in severe haemophilia A since 1990 attributable to more low titre inhibitors

van den Berg, H. Marijke; Hashemi, S. Mojtaba; Fischer, Kathelijn; Petrini, Pia; Ljung, Rolf LU ; Rafowicz, Anne; Carcao, Manuel; Auerswald, Günter; Kurnik, Karin and Kenet, Gili, et al. (2016) In Thrombosis and Haemostasis 115(4). p.729-737
Abstract

Many studies have reported an increased incidence of inhibitors in previously untreated patients (PUPs) with severe haemophilia A after the introduction of recombinant products. It was the objective of this study to investigate whether the inhibitor incidence has increased between 1990 and 2009 in an unselected cohort of PUPs with severe haemophilia A (FVIII<1 %). Patients were consecutively recruited from 31 haemophilia treatment centres in 16 countries and followed until 50 exposure days or until inhibitor development. Inhibitor development was studied in five-year birth cohorts comparing cumulative incidences. Furthermore the risk for inhibitor development per fiveyear birth cohort was studied using multivariable Cox regression,... (More)

Many studies have reported an increased incidence of inhibitors in previously untreated patients (PUPs) with severe haemophilia A after the introduction of recombinant products. It was the objective of this study to investigate whether the inhibitor incidence has increased between 1990 and 2009 in an unselected cohort of PUPs with severe haemophilia A (FVIII<1 %). Patients were consecutively recruited from 31 haemophilia treatment centres in 16 countries and followed until 50 exposure days or until inhibitor development. Inhibitor development was studied in five-year birth cohorts comparing cumulative incidences. Furthermore the risk for inhibitor development per fiveyear birth cohort was studied using multivariable Cox regression, adjusting for potential genetic and treatment-related confounders. A total of 926 PUPs were included with a total cumulative inhibitor incidence of 27.5 %. The inhibitor incidence increased from 19.5 % in 1990–1994 (lowest) to 30.9 % in 2000–2004 (highest; p-value 0.011). Low titre inhibitor incidence increased from 3.1 % in 1990–1994 to 10.5 % in 2005–2009 (p-value 0.009). High titre inhibitor incidences remained stable over time. After 2000, risk of all inhibitor development was increased with adjusted hazard ratios 1.96 (95 % CI 1.06–2.83) in 2000–2004 and 2.34 (1.42–4.92) in 2005–2009. Screening for inhibitors was intensified over this 20-year study period from a median of 1.9 to 2.9 tests/year before 2000 to 2.7 to 4.3 tests/ year after 2000. In conclusion, the cumulative inhibitor incidence has significantly increased between 1990 and 2009. The high titre inhibitor incidence has remained stable.

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publication status
published
subject
keywords
Epidemiological studies, Factor VIII inhibitors, Haemophilia A / B, Risk factors
in
Thrombosis and Haemostasis
volume
115
issue
4
pages
9 pages
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • Scopus:84964720994
  • WOS:000373862900003
ISSN
0340-6245
DOI
10.1160/TH15-08-0692
language
English
LU publication?
yes
id
6f50592a-1f69-4fc8-b431-b35cc27541c2
date added to LUP
2016-06-29 15:47:07
date last changed
2017-01-08 05:56:01
@article{6f50592a-1f69-4fc8-b431-b35cc27541c2,
  abstract     = {<p>Many studies have reported an increased incidence of inhibitors in previously untreated patients (PUPs) with severe haemophilia A after the introduction of recombinant products. It was the objective of this study to investigate whether the inhibitor incidence has increased between 1990 and 2009 in an unselected cohort of PUPs with severe haemophilia A (FVIII&lt;1 %). Patients were consecutively recruited from 31 haemophilia treatment centres in 16 countries and followed until 50 exposure days or until inhibitor development. Inhibitor development was studied in five-year birth cohorts comparing cumulative incidences. Furthermore the risk for inhibitor development per fiveyear birth cohort was studied using multivariable Cox regression, adjusting for potential genetic and treatment-related confounders. A total of 926 PUPs were included with a total cumulative inhibitor incidence of 27.5 %. The inhibitor incidence increased from 19.5 % in 1990–1994 (lowest) to 30.9 % in 2000–2004 (highest; p-value 0.011). Low titre inhibitor incidence increased from 3.1 % in 1990–1994 to 10.5 % in 2005–2009 (p-value 0.009). High titre inhibitor incidences remained stable over time. After 2000, risk of all inhibitor development was increased with adjusted hazard ratios 1.96 (95 % CI 1.06–2.83) in 2000–2004 and 2.34 (1.42–4.92) in 2005–2009. Screening for inhibitors was intensified over this 20-year study period from a median of 1.9 to 2.9 tests/year before 2000 to 2.7 to 4.3 tests/ year after 2000. In conclusion, the cumulative inhibitor incidence has significantly increased between 1990 and 2009. The high titre inhibitor incidence has remained stable.</p>},
  author       = {van den Berg, H. Marijke and Hashemi, S. Mojtaba and Fischer, Kathelijn and Petrini, Pia and Ljung, Rolf and Rafowicz, Anne and Carcao, Manuel and Auerswald, Günter and Kurnik, Karin and Kenet, Gili and Santagostino, Elena},
  issn         = {0340-6245},
  keyword      = {Epidemiological studies,Factor VIII inhibitors,Haemophilia A / B,Risk factors},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {729--737},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Increased inhibitor incidence in severe haemophilia A since 1990 attributable to more low titre inhibitors},
  url          = {http://dx.doi.org/10.1160/TH15-08-0692},
  volume       = {115},
  year         = {2016},
}