Preference for Emicizumab over Prior Factor Treatments: Results from the HAVEN 3 and HAVEN 4 Studies

Background Hemophilia A with or without inhibitors to factor VIII (FVIII) has a major impact on the quality of life of people with this condition. This may be exacerbated by the treatment burden associated with current factor treatments that require frequent IV administration to reduce the risk of bleeding. Previous studies have noted that patients favor treatments that have a goal of achieving a “normal life” and avoid negative effects (e.g. infusion-related pain, time-consuming, or high treatment burden) (Cimino et al. Patient Prefer Adherence 2014). Two Phase III studies recently demonstrated the efficacy and safety of subcutaneous emicizumab administered weekly (QW) or every 2 weeks (Q2W) in persons with hemophilia A (PwHA) without inhibitors (HAVEN 3; NCT02847637; Mahlangu et al. N Engl J Med 2018, in press), and every 4 weeks (Q4W) in PwHA with or without inhibitors (HAVEN 4; NCT03020160; Pipe et al. WFH 2018). The studies included questionnaires developed and validated to investigate patients' preference and satisfaction with emicizumab compared with prior treatment. Methods In HAVEN 3, PwHA without inhibitors aged ≥12 years on prior episodic FVIII were randomized 2:2:1 to receive emicizumab QW (Arm A), Q2W (Arm B), or to no prophylaxis control (Arm C). Patients on prior prophylactic FVIII received emicizumab QW (Arm D). In HAVEN 4, PwHA with or without inhibitors aged ≥12 years with prior episodic bypassing agents (BPAs) or prophylactic FVIII received emicizumab Q4W. Patient preference was assessed through the Emicizumab Preference Survey (EmiPref) at Week 17 in both studies when patients had gained sufficient experience with emicizumab, potential bias due to anticipation associated with being in a study subsided, and they could still reliably recall their experience with prior therapy. The survey included three questions: patients were initially asked which they preferred - previous hemophilia treatment, new study treatment, or no preference. Those expressing a preference were then asked to rank the top three reasons for their choice. Finally, patients could provide additional free text related to their experience with emicizumab. Treatment satisfaction was assessed in Arm D of HAVEN 3 using the Satisfaction Questionnaire - Intravenous Subcutaneous Hemophilia Injection (SQ-ISHI). This 16-item questionnaire was to be completed at baseline and then either Week 21 or 25 after initiation of emicizumab. Results EmiPref was completed by 95/134 patients