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. 2023 Jan-Dec:29:10760296231167416.
doi: 10.1177/10760296231167416.

Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII

Louise H Hooimeijer  1 , Marjet A Stein-Wit  1 , Marja Aj Voskuilen  2 , Michaël V Lukens  3 , Karina Meijer  2 , Anja Bu Mäkelburg  2 , Rienk Yj Tamminga  1
Affiliations

Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII

Louise H Hooimeijer et al. Clin Appl Thromb Hemost. 2023 Jan-Dec.

Abstract

In 2018, Refacto AFR, a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AFR; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 > 0.6 BU, 1 high titre) after they switched to Refacto AFR; all were children <14 years of age and with >100 exposure days, none related to surgery or intensive treatment; all received KovaltryR before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AFR is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding KovaltryR might have contributed to inhibitor development.

Keywords: antibodies; factor VIII concentrate; hemophilia A; immunity; therapeutics.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Meijer reports speaker fees from Alexion, Bayer, and CSL Behring, participation in trial steering committee for Bayer, consulting fees from Uniqure, and participation in data monitoring and endpoint adjudication committee for Octapharma. All fees are paid to her institution. None of the other authors has a potential conflict of interest.

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