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

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.