Background: Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited. Objectives: To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B. Methods: Inhibitor development in PTPs was collected since 2008 from 97 centers participating in European HAemophilia Safety Surveillance. Per concentrate, inhibitors were reported quarterly and the number of PTPs treated annually. Incidence rates (IRs)/1000 treatment years with 95% CIs were compared between concentrate types (plasma derived FVIII/FIX, standard half-life recombinant FVIII/FIX, and extended half-life recombinant (EHL-rFVIII/IX) concentrates using IR ratios with CI. Medians and IQRs were calculated for inhibitor characteristics. Results: For severe haemophilia A, inhibitor rate was 66/65,200 treatment years, IR 1.00/1000 years (CI 0.80-1.30), occurring at median 13.5 years (2.7-31.5) and 150 EDs (80-773). IR on plasma-derived pdFVIII (IR, 1.13) and standard half-life recombinant FVIII (IR, 1.12) were similar, whereas IR on EHL-rFVIII was lower at 0.13 (incidence rate ratio, 0.12; 95% CI, <0.01-0.70; P < .01).For severe hemophilia B, inhibitor rate was 5/11,160 treatment years and IR was 0.45/1000 years (95% CI, 0.15-1.04), at median 3.7 years (95% CI, 2.1-42.4) and 260 EDs (95% CI, 130 to >1000). Data were insufficient to compare by type of FIX concentrates. Conclusion: Low inhibitor rates were observed for PTPs with severe hemophilia A and B. Data suggested reduced inhibitor development on EHL-rFVIII, but no significant difference between plasma-derived FVIII and standard half-life recombinant FVIII. FIX inhibitor rates were too low for robust statistical analysis.
Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS) / K. Fischer, R. Lassila, F. Peyvandi, A. Gatt, S.C. Gouw, R. Hollingsworth, T. Lambert, R. Kaczmarek, D. Carbonero, M. Makris, C. Ay, C. Male, C. Hermans, P. Verhamme, T. Lissitchkov, M. Antoniades, M. Penka, J. Blatny, V. Komrska, L.H. Poulsen, P. Kampmann, A. Lehtinen, S. Susen, Y. Dargaud, C. Biron, R. D'Oiron, A. Harroche, R. Klamroth, J. Oldenburg, M. Buehrlen, W. Miesbach, F. Langer, P. Spannag, M. Oliveri, H. Platokouki, E. Nomikou, O. Katsarou, V. Garypidou, M. Economou, L. Nemes, B. Nolan, N. O'Connell, R. Paolo, G. Castaman, F. Peyvandi, A. Rocino, E. Zanon, A. Tagliaferri, G. Agnelli, R. De Crisotofaro, P. Schinco, A. Tosetto, S. Lejniece, N. Gailiute, A. Gatt, A. Mäkelburg, B. Laros-van Gorkom, P. Brons, F.W.G. Leebeek, R. Schutgens, J. Windyga, C. Catarino, A. Aires, C. Fraga, S. Morais, F. Araújo, M. Serban, I. Davydkin, A. Batorova, S. Anzej Doma, L.S. Martinez, A. Palomo Bravo, I.S. Ortega, S. Bonanad, F. Baghaei, J. Astermark, M. Holmström, P. Fontana, M. Schmugge, B. Zulfikar, K. Kavakli, M. Khan, G. Benson, W. Lester, P. Andrew, B. Catherine, F. Pinto, S. Salta, C. Farrelly, M. Matthias, M. Laffan, Y. Thynn Thynn, V. Mcdonald, S. Austin, M. Bella, C. Hay, J. Grainger, K. Talks, S. Shapiro, R. Maclean, J. Payne. - In: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS. - ISSN 2475-0379. - 8:4(2024), pp. 102461.1-102461.7. [10.1016/j.rpth.2024.102461]
Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS)
F. Peyvandi;G. Agnelli;
2024
Abstract
Background: Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited. Objectives: To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B. Methods: Inhibitor development in PTPs was collected since 2008 from 97 centers participating in European HAemophilia Safety Surveillance. Per concentrate, inhibitors were reported quarterly and the number of PTPs treated annually. Incidence rates (IRs)/1000 treatment years with 95% CIs were compared between concentrate types (plasma derived FVIII/FIX, standard half-life recombinant FVIII/FIX, and extended half-life recombinant (EHL-rFVIII/IX) concentrates using IR ratios with CI. Medians and IQRs were calculated for inhibitor characteristics. Results: For severe haemophilia A, inhibitor rate was 66/65,200 treatment years, IR 1.00/1000 years (CI 0.80-1.30), occurring at median 13.5 years (2.7-31.5) and 150 EDs (80-773). IR on plasma-derived pdFVIII (IR, 1.13) and standard half-life recombinant FVIII (IR, 1.12) were similar, whereas IR on EHL-rFVIII was lower at 0.13 (incidence rate ratio, 0.12; 95% CI, <0.01-0.70; P < .01).For severe hemophilia B, inhibitor rate was 5/11,160 treatment years and IR was 0.45/1000 years (95% CI, 0.15-1.04), at median 3.7 years (95% CI, 2.1-42.4) and 260 EDs (95% CI, 130 to >1000). Data were insufficient to compare by type of FIX concentrates. Conclusion: Low inhibitor rates were observed for PTPs with severe hemophilia A and B. Data suggested reduced inhibitor development on EHL-rFVIII, but no significant difference between plasma-derived FVIII and standard half-life recombinant FVIII. FIX inhibitor rates were too low for robust statistical analysis.
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