Management of Persons with Hemophilia A with Inhibitors After Emicizumab Approval

Introduction: Emicizumab, a bispecific antibody to factors IXa/X, was approved by the Food and Drug Administration in 2017 for prophylactic treatment of persons with hemophilia A (PwHA) with inhibitors. Compared with other treatments for PwHA, emicizumab has a novel mechanism of action. It is the first hemophilia A (HA) treatment administered subcutaneously and has a much longer half-life than previous treatments; hence, disease management with emicizumab can be different. This study aimed to evaluate how physicians manage HA in patients treated with emicizumab.

Methods: This qualitative analysis is the first phase of a planned mixed-methods approach study and comprised 1-hour, blinded telephone interviews with 5 hematologists in all 4 geographic regions of the US. Physicians were included if they met the following criteria: 1) MD or DO degree; 2) board-certified hematologist; 3) practice in the US; 4) ≥2 years of experience post-residency; and 5) currently treat PwHA. To evaluate experience with emicizumab, physicians were also required to have treated a minimum number of patients receiving emicizumab (5 for physicians in hemophilia treatment centers [HTCs] and 3 for physicians in non-HTCs). A total of 5 qualitative interviews were conducted in May and June 2018 to understand the physicians' perspectives on treating PwHA with emicizumab. Interview topics included general management of PwHA, inhibitor screening and testing, management of PwHA with inhibitors, and physicians' experiences treating patients with emicizumab. We report common themes that descriptively emerged from the qualitative interviews, which will inform survey development for the quantitative phase of the study.

Results: Of the 5 physicians, 3 were adult hematologists and 4 physicians reported seeing patients in an HTC. All physicians reported having at least 10 years of experience in practice post-residency. Regarding management of PwHA, physicians indicated disease severity, inhibitor status and annual bleed rate as critical factors in guiding treatment decision making. Patients who develop inhibitors require more medical engagement and frequent monitoring. Physicians reported that, from their experience, emicizumab results in a reduction in bleeds, leading to fewer office visits and less monitoring in PwHA with inhibitors. In addition, physicians reported that the need for disease management, even among patients with a phenotype with more bleeding, is lower as a result of emicizumab treatment due to decreased bleed rate and a reduction in need for additional treatments. Physicians reported that emicizumab's subcutaneous, once-weekly dosing leads to improved patients' quality of life and confidence in performing activities without bleeds. Acute bleed management with emicizumab was reported to be slightly different than before, given the boxed warning around concomitant treatment with activated prothrombin complex concentrate; however, the physicians indicated that they still recommend to treat bleeds as soon as one is suspected. Physicians articulated that some questions remain, including the role of immune therapy induction (ITI), use in low-titer inhibitors, and surgical management in patients treated with emicizumab. Physicians reported that there have been no significant access challenges and none of their patients have discontinued therapy; however, long-term monitoring and safety data are needed.

Conclusions: This qualitative study suggests that management of PwHA with inhibitors receiving emicizumab is evolving. The interviewed physicians reported that their patients receiving emicizumab experience fewer bleeds and have an improved quality of life. However, questions regarding the role of ITI, surgical management, and long-term safety of emicizumab remain. Future research will provide additional insights into the current management of PwHA with inhibitors treated with emicizumab among US physicians.