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. 2024 May 27;8(4):102461.
doi: 10.1016/j.rpth.2024.102461. eCollection 2024 May.

Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS)

Kathelijn Fischer  1 , Riitta Lassila  2 , Flora Peyvandi  3   4 , Alexander Gatt  5 , Samantha C Gouw  6   7 , Rob Hollingsworth  8 , Thierry Lambert  9 , Radek Kaczmarek  10   11 , Diana Carbonero  12 , Mike Makris  13 ; European HAemophilia Safety Surveillance (EUHASS) participants
Collaborators, Affiliations

Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS)

Kathelijn Fischer et al. Res Pract Thromb Haemost. .

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.

Keywords: PTP; antibodies; factor VIII; hemophilia A; hemophilia B; inhibitor; neutralizing factor; registries.

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Figures

Figure
Figure
Age at inhibitor development after 50 exposure days according to diagnosis.
See this image and copyright information in PMC

References

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    1. Male C., Andersson N.G., Rafowicz A., Liesner R., Kurnik K., Fischer K., et al. Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study. Haematologica. 2021;106:123–129. - PMC - PubMed
    1. Fischer K., Iorio A., Hollingsworth R., Makris M., EUHASS collaborators. FVIII inhibitor development according to concentrate: data from the EUHASS registry excluding overlap with other studies. Haemophilia. 2016;22:e36–e38. - PubMed
    1. Fischer K., Lassila R., Peyvandi F., Calizzani G., Gatt A., Lambert T., et al. Inhibitor development in haemophilia according to concentrate: four-year results from the European HAemophilia Safety Surveillance (EUHASS) project. Thromb Haemost. 2015;113:968–975. - PubMed
    1. Gouw S.C., Van Der Bom J.G., Ljung R., Escuriola C., Cid A.R., Claeyssens-Donadel S., et al. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med. 2013;368:231–239. - PubMed

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