Incidence of inhibitor development in PUPs with severe Haemophilia A in the CEE region between 2005 and 2015

BLATNÝ, Jan, Maria KARDOS, Predrag MILJIC, Ernest BILIC, Majda BENEDIK-DOLNICAR, Barbara FAGANEL-KOTNIK, Dobrin KONSTANTINOV, Zhanna KOVALOVA and Petra OVESNÁ. Incidence of inhibitor development in PUPs with severe Haemophilia A in the CEE region between 2005 and 2015. Thrombosis Research. OXFORD: Pergamon-Elsevier Science, 2021, vol. 198, FEB 2021, p. 196-203. ISSN 0049-3848. Available from: https://dx.doi.org/10.1016/j.thromres.2020.12.004.

Basic information

• Original name: Incidence of inhibitor development in PUPs with severe Haemophilia A in the CEE region between 2005 and 2015
• Authors: BLATNÝ, Jan (203 Czech Republic, guarantor, belonging to the institution), Maria KARDOS, Predrag MILJIC, Ernest BILIC, Majda BENEDIK-DOLNICAR, Barbara FAGANEL-KOTNIK, Dobrin KONSTANTINOV, Zhanna KOVALOVA and Petra OVESNÁ (203 Czech Republic, belonging to the institution).
• Edition: Thrombosis Research, OXFORD, Pergamon-Elsevier Science, 2021, 0049-3848.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30205 Hematology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 10.407
• RIV identification code: RIV/00216224:14110/21:00121759
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1016/j.thromres.2020.12.004
• UT WoS: 000616053200031
• Keywords in English: Haemophilia A; Inhibitors; CEE; Cohort studies; Risk factors; PUPs
• Tags: 14110321, 14119612, rivok
• Tags: International impact, Reviewed

Abstract

Introduction: This study analyses real-world data on 144 previously untreated patients (PUPs) with severe Haemophilia A, from seven countries in Central and Eastern Europe (CEE: Bulgaria, Croatia, Czech Republic, Hungary, Latvia, Serbia, and Slovenia), over a period of 11 years. It analyses the risk factors associated with development of inhibitors to factor VIII concentrates. Methods: Cox proportional hazard models were used to estimate the hazard risk of factors possibly influencing the development of inhibitors. Patients were followed for up to 100 exposure days (EDs). Results: Cumulative inhibitor incidence at the time of 100 EDs was 18.7%, slightly lower than the 25-35% incidence reported in most studies. Of PUPs who developed inhibitors, a majority (56%) developed them within the first 20 EDs and 88% by the 50th ED. FVIII class (recombinant or plasma-derived) did not influence the inhibitors' incidence rate (p = 0.64). We found a significant protective effect of prophylaxis compared to on demand treatment (p = 0.003). PUPs who had an intensive peak treatment during the first 50 EDs were at significantly higher risk for inhibitor development (HR (95% CI) 5.3 (2.3-12.5), p < 0.001). Conclusion: Inhibitors are and will continue to be the most significant complication of haemophilia treatment with factor concentrates. This is particularly true for haemophilia A. In our cohort, we were able to show that the treatment regimen used during first 50EDs influenced significantly the inhibitor risk, but the class of the factor concentrate did not play an important role. Real world data will remain one of the important resources for improving our knowledge of haemophilia.