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Inhibitor development in previously untreated patients with severe haemophilia A: a nationwide multicentre study in Finland
Author(s) -
Vepsäläinen K.,
Lassila R.,
Arola M.,
Huttunen P.,
Koskinen S.,
Ljung R.,
Lähteenmäki P.,
Möttönen M.,
Riikonen P.
Publication year - 2016
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.12974
Subject(s) - medicine , haemophilia , bleed , incidence (geometry) , haemophilia a , pediatrics , cumulative incidence , venous access , clinical endpoint , titer , cohort , surgery , antibody , immunology , clinical trial , physics , catheter , optics
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 ( PUP s) with severe haemophilia A ( FVIII :C < 0.01 IU mL −1 ). Methods We enrolled all PUP s ( N = 62) born between June 1994 and May 2013 with at least 75 exposure days ( ED s) 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 ED s. 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.