Reappearance of inhibitor in a tolerized patient with severe haemophilia A during FVIII‐free emicizumab therapy

Introduction: The recent approval of emicizumab has significantly changed the management of severe hemophilia A. It also raises several questions, particularly concerning the need to maintain FVIII infusion in emicizumab-treated patients after successful ITI. Indeed, the possible reappearance of the inhibitor is a major concern, while, to date, no recurrence of the inhibitor has been observed in successfully tolerized patients. Aim: To describe the reappearance of an inhibitor in a successfully tolerized patient with severe hemophilia A during emicizumab therapy alone (in the absence of any exposure to FVIII), and to discuss the benefit in maintaining FVIII infusion.Methods: Case reportResults: We report on a case in which inhibitor production spontaneously reappeared more than 7 years after successful ITI and 4 months after emicizumab initiation and FVIII withdrawal. Indeed, the patient was inhibitor-negative one month after emicizumab initiation and despite the absence of any FVIII infusions, a low positive titer was observed 4 months later together with reemergence of both anti-FVIII IgG1 and IgG4.Conclusion: Our observation supports the hypothesis whereby regular exposure to FVIII may be necessary to maintain successful, specific immune tolerance. Therefore, emicizumab-treated patients with a history of inhibitor, even those not exposed to FVIII, should be regularly screened for the presence of an inhibitor.