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Inhibitor development in previously untreated patients with severe haemophilia A: a nationwide multicentre study in Finland
- Source :
- Haemophilia. 22:721-729
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
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 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. (Less)
- Subjects :
- Male
medicine.medical_specialty
Pediatrics
Genotype
Haemophilia A
Hemorrhage
030204 cardiovascular system & hematology
Hemophilia A
Haemophilia
Severity of Illness Index
03 medical and health sciences
0302 clinical medicine
Risk Factors
Internal medicine
Humans
Medicine
Cumulative incidence
Finland
Genetics (clinical)
Proportional Hazards Models
Retrospective Studies
Factor VIII
Hematology
Coagulants
business.industry
Incidence (epidemiology)
Infant, Newborn
Infant
General Medicine
ta3121
Bleed
medicine.disease
Antibodies, Neutralizing
3. Good health
Child, Preschool
Complication
business
030215 immunology
Subjects
Details
- ISSN :
- 13518216
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Haemophilia
- Accession number :
- edsair.doi.dedup.....3ba4cc3663f39f219af73db8509b32e3