D3.437 - Impact of benralizumab on fatigue and health-related quality of life in patients with hypereosinophilic syndrome: findings from the NATRON phase 3 trial

Hypereosinophilic syndrome (HES) is a group of rare, heterogenous disorders characterized by persistent hypereosinophilia and eosinophil-mediated end-organ damage. Fatigue is a common symptom of HES, which can adversely impact health-related quality of life (HRQoL). Benralizumab has demonstrated efficacy in HES in the NATRON trial, with reductions in flares and improvements in fatigue following 24 weeks of treatment. Here, we report post-hoc analyses examining the relationship between fatigue and HRQoL from NATRON.

NATRON (NCT04191304) was a phase 3, randomized, double-blind, placebo-controlled study in patients with FIP1L1::PDGFRA-negative HES. Fatigue severity was assessed by an investigator-led symptom interview and the PROMIS Fatigue SF-7, and HRQoL was assessed using the SF-36v2. A sub-group analysis was performed in patients with higher fatigue scores at baseline (PROMIS Fatigue score >55). Pearson’s correlation was used to assess the linear correlation between PROMIS Fatigue and SF-36v2.

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). Based on investigator-led interview, a higher percentage of patients in the benralizumab group achieved absence of fatigue compared with placebo (69.2% and 47.5%) at week 24, respectively (Figure). In a subgroup analysis of patients with higher fatigue scores at baseline (>55; benralizumab, n=34; placebo, n=37), PROMIS Fatigue scores were significantly improved in the benralizumab group versus placebo at Week 24: least squares mean difference –7.12 (95% CI: –11.20, –3.04; p=0.0009). The proportion of patients with a PROMIS Fatigue score >55 at baseline achieving a ≥6- or ≥13-point improvement in PROMIS Fatigue score was 76.5% and 55.9% with benralizumab and 43.9% and 14.6% with placebo, respectively. Improvements in PROMIS Fatigue scores were highly correlated with SF-36 improvements in Vitality (benralizumab: -0.845, placebo: -0.824), Role Limitations due to Physical Health (benralizumab: -0.650, placebo: -0.601), and the Physical Component Score (benralizumab: -0.562, placebo: -0.658).

Benralizumab consistently improved fatigue across multiple assessments in patients with HES. Improvements in fatigue correlated with improved HRQoL in patients, suggesting that improving this common manifestation of HES with a targeted therapy can improve other aspects of HRQoL.