Abstract Rationale Hypereosinophilic syndrome (HES) is a group of rare, heterogenous disorders characterized by persistent hypereosinophilia and eosinophil-mediated end-organ damage. Benralizumab, an anti-IL-5 receptor α antibody, causes near-complete depletion of eosinophils and has demonstrated positive results in the NATRON phase 3 trial in patients with HES. Here, we report the effect of benralizumab on health-related quality of life (HRQoL) using the Short Form-36 (SF-36). Methods NATRON (NCT04191304) is a phase 3, randomized, double-blind, multicenter, placebo-controlled study, designed to evaluate the efficacy and safety of benralizumab in patients with FIP1L1::PDGFRA-negative HES. HRQoL, assessed with SF-36 version 2, was a prespecified secondary endpoint. SF-36 includes eight subscales (0-100 scale; higher scores indicate better HRQoL): physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). Patients were deemed ‘responders’ if their subscale score changes from baseline met or exceeded minimal clinically important difference thresholds (PF 4.3; RP 3.4; BP 6.2; GH 7.2; VT 6.2; SF 6.9; RE 4.5; MH 6.2). P-values were not adjusted for multiplicity, and therefore nominal significance levels are reported. Results Overall, 133 patients (median age 51 range 14-87 years; 61.7% female) were randomized 1:1 to benralizumab 30 mg Q4W (n = 67) or placebo (n = 66). At Week 12, benralizumab showed significant improvements across all SF-36 subscales; improvements were sustained to Week 24 for most subscales (Figure 1). Least squares mean differences (95% CI) from baseline to Week 24 were: PF, 4.40 (2.0, 6.8; p = 0.0004); RP, 5.02 (2.1, 7.9; p = 0.0008); BP 3.54 (0.5, 6.6; p = 0.0238); GH, 3.71 (0.9, 6.5; p = 0.0093); VT, 4.48 (1.4, 7.5; p = 0.0043); SF, 2.78 (0.0, 5.5; p = 0.0479); RE, 3.32 (-0.1, 6.7; p = 0.535); MH, 2.83 (-0.2, 5.8; p = 0.0629). Responder analyses at Week 24 numerically favored benralizumab versus placebo for all subscales; significance (OR; 95% CI) was observed for RP (3.31; 1.34, 8.13; p = 0.0092), GH (4.12; 1.55, 10.96; p = 0.0046), and VT (2.55; 1.09, 5.95; p = 0.0311). Conclusion In patients with HES, benralizumab improved HRQoL versus placebo, with improvements across all SF-36 subscales by Week 12, sustained through Week 24 for most subscales. These improvements, alongside demonstrated clinical efficacy in the primary analysis, indicate consistent effects of benralizumab on patient functioning and well-being. This is the first report of a treatment for HES associated with improvements in a validated HRQoL measure. This abstract is funded by: The study is sponsored and funded by AstraZeneca (Södertälje, Sweden). This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH author(s) were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.
Akuthota et al. (Fri,) studied this question.