Patient perspectives on the burden of hypereosinophilic syndrome: Results from the Phase 3 natron interview sub-study

Abstract Background Hypereosinophilic syndrome (HES) encompasses a group of rare disorders characterized by persistently high levels of eosinophils that confer end-organ damage and dysfunction. While HES signs, symptoms, and health-related quality of life (HRQoL) impacts are known to be heterogeneous, and this heterogeneity impedes diagnosis and treatment, the diversity of experiences that patients with HES report is poorly documented in the literature. Here, we report symptoms and HRQoL impacts described by patients in the qualitative interview sub-study of an interventional trial. Methods NATRON (NCT04191304) is a phase 3, multicenter, randomized, 24-week, double-blind (DB), placebo-controlled trial evaluating the efficacy and safety of benralizumab in patients with FIP1L1::PDGFRA-negative HES. In the sub-study reported here, interested NATRON patients in Poland (n=21) and the US (n=8) participated in a telephone interview lasting ~90 minutes. Interviews followed a semi-structured discussion guide and were scheduled between 7 and 21 days after the last dose of DB treatment. Topics discussed included HES diagnosis journey, HES-associated signs and symptoms, reasons for participating in the study, expectations related to joining the study, and personal definitions of treatment success. Results Of the 29 patients who participated in the interview, the majority were female (89.7%, n=26). All patients were White (100%, n=29). Among patients who reported their educational attainment, 34.5% (n=10) had a high school education or less, 24.1% (n=7) had a bachelor's degree, 17.2% (n=5) held a graduate degree, and 13.8% (n=4) selected “other”. Mean (standard deviation [SD]) age was 48.6 (16.6) years, with a mean (SD) time since diagnosis of 36.5 (40.4) months. Patients reported experiencing 60 signs and symptoms related to HES, which were organized into 13 domains during the analysis. The pulmonary/respiratory, constitutional, sinonasal, dermatological, musculoskeletal, and neurological domains had signs or symptoms reported by more than 70% of patients. Symptoms reported by more than 50% of patients were coughing (75.9%, n=22), shortness of breath (72.4%, n=21), and wheezing (69.0%, n=20) in the pulmonary/respiratory domain; fatigue (79.3%, n=23), weakness (65.5%, n=19), malaise (58.6%, n=17), and chills/sweats (51.7%, n=15) in the constitutional domain; nasal congestion (69.0%, n=20), runny nose (55.2%, n=16), and sneezing (55.2%, n=16) in the sinonasal domain; itching (69.0%, n=20) in the dermatological domain; and muscle ache/pain (51.7%, n=15) and joint ache/pain (51.7%, n=15) in the musculoskeletal domain. The most frequently reported HRQoL impacts of HES were general activities of daily living (ADL) (82.8%, n=24; ADL domain), difficulty sleeping (62.1%, n=18; ADL domain), physical activity (75.9%, n=22; physical domain), social life (69.0%, n=20; social domain), and work impacts (51.7%, n=15; functional domain). Reasons for participating in the study included to improve their health situation (75.9%, n=22), to avoid systemic corticosteroid use (34.5%, n=10), to seek alternative treatment (20.7%, n=6), because of physician recommendation (17.2%, n=5), and to help others with HES (3.4%, n=1). The most commonly reported expectations from study participation were to enhance health (55.2%, n=16) and/or quality of life (17.2%, n=5), and other expectations such as reducing or stopping steroid use and/or experiencing minimal side effects (17.2%, n=5). Finally, the most common definitions of success were improvement in/reduction of symptoms (27.6%, n=8), complete resolution of signs and symptoms (10.3%, n=3), and finding an effective treatment other than systemic corticosteroids (6.9%, n=2). Conclusions Patients with HES experience a broad range of signs and symptoms, with specific impacts on ADL and physical well-being. The findings of this sub-study underscore the high burden of HES symptoms and suggest an urgent need for timely diagnosis and targeted treatment. Additional research on patients' experiences of living with HES and with HES treatment is warranted, and further planned analyses aim to expand on these findings.