Efficacy of benralizumab in reducing cough and/or dyspnea frequency, and improving cough-specific health-related quality of life in patients with severe eosinophilic asthma in Asia.

Biologics' efficacy in relieving cough and dyspnea in severe eosinophilic asthma (SEA) is under-characterized. This exploratory analysis evaluated the efficacy of benralizumab separately in reducing cough and/or dyspnea in patients with SEA. Post-hoc analysis of a phase III, randomized, double-blind, placebo-controlled trial. MIRACLE (NCT03186209) data were used, involving patients aged 12-75 years with uncontrolled SEA. Patients reporting baseline frequent cough and/or dyspnea based on St George's Respiratory Questionnaire (SGRQ) items were analyzed. Changes in cough frequency, cough-specific HRQoL, and dyspnea frequency measured through relevant SGRQ items were evaluated over 48 weeks. Subgroup analyses based on baseline blood eosinophil counts (bEOS ⩾300 cells/μL) were conducted. A total of 383 patients (benralizumab: 189; placebo: 194) with baseline frequent cough and 304 with baseline frequent dyspnea (benralizumab: 151; placebo: 153) were included. The proportions of patients transitioning to non-frequent cough with benralizumab versus placebo were 54.0% versus 39.7% at Week 8 (p = 0.0051), and 59.3% versus 56.7% at Week 48. Improvements in cough-related SGRQ items, including reductions in cough-related pain/fatigue, less sleep disturbance, and decreased embarrassment in public, occurred earlier with benralizumab compared to placebo and were sustained through Week 48. Among patients with higher inflammatory burden (baseline bEOS ⩾300 cells/μL), the prevalence of frequent cough at baseline was higher. In this subgroup, a higher proportion transitioned to non-frequent cough with benralizumab versus placebo at both Week 8 (55.3% vs 37.1%; p = 0.0027) and Week 48 (59.8% vs 52.1%). Differential improvements in cough-related SGRQ items favoring benralizumab were consistently observed. Reductions in dyspnea frequency followed a similar pattern, with benralizumab showing greater improvements versus placebo at both Week 8 (64.2% vs 47.1%; p = 0.0026) and Week 48 (75.5% vs 63.4%; p = 0.0221). Benralizumab showed potential to rapidly reduce cough and/or dyspnea frequency, and to improve cough-specific HRQoL more quickly than placebo in patients with SEA, with sustained advantage in cough-related SGRQ items through Week 48. Improvements were pronounced in patients with higher baseline bEOS, potentially reflecting a higher disease burden. However, as this was an exploratory analysis, further validation using cough-specific clinical endpoints is warranted. ClinicalTrials.gov, NCT03186209, https://clinicaltrials.gov/study/NCT03186209.