No immunological changes after factor VIII product switch: An in-depth analysis in haemophilia A patients

Authors: Schep, SJ; Fischer, K; Boes, M; Schutgens, RE

Affiliations: Univ Utrecht, Univ Med Ctr Utrecht, Ctr Benign Haematol Thrombosis & Haemostasis, Van Creveldkliniek, Utrecht, Netherlands. Univ Utrecht, Univ Med Ctr Utrecht, Ctr Translat Immunol CTI, Utrecht, Netherlands. Univ Utrecht, Univ Med Ctr Utrecht, Pediat Dept, Utrecht, Netherlands. Univ Utrecht, Univ Med Ctr Utrecht, Van Creveldkliniek, Huispost C01 428, Postbus 85500, NL-3508 GA Utrecht, Netherlands

Publication: Haemophilia; 2023

Abstract: BACKGROUND A challenging complication in the treatment of haemophilia A is the formation of neutralizing anti-FVIII antibodies (inhibitors). There is ongoing debate on the effect of FVIII product and inhibitor risk, rendering patients and physicians reluctant to switch FVIII-products. AIM This study aimed to evaluate changes in the immune profile of haemophilia A patients after switching FVIII products and their possible relation to inhibitor development. Secondary, FVIII efficacy after switching were assessed. METHODS Patients, who switched FVIII-products between 2017-2019, were included in this single centre cohort study. Prospective comparison of immunoregulatory cells and markers by flow-cytometry before and after the switch was performed in a subgroup. For the total cohort clinical data regarding inhibitor development and FVIII efficacy 1 year before and after switching were retrospectively collected. RESULTS One-hundred patients (including 39 with prospective immunological assessment) were analyzed, of which 31% switched from plasma-derived (pdFVIII) to recombinant standard half-life FVIII (SHL-rFVIII), 47% between different SHL-rFVIII, and 22% from pdFVIII/SHL-rFVIII to rFVIII-Fc. No remarkable changes in immunoregulatory cell functions were observed after switching, regardless the type of switch. None of the patients developed an inhibitor. FVIII efficacy, that is, FVIII usage, half-life and annual bleeding rate (ABR), was similar before and after switch for the SHL products, whereas rFVIII-Fc associated with a longer half-life (13.1 vs. 15.0 h) and lower ABR (3.0 vs. 1.0). CONCLUSIONS Switching to a different FVIII product was not associated with inhibitor development, nor with differences in the immune profile. Switching to rFVIII-Fc lead to lower ABR.