Mepolizumab fails to improve refractory chronic cough in small eosinophilic airways disease trial

OBJECTIVE: Patients presenting with chronic cough often have eosinophilic airways disease that remains refractory despite inhaled or oral corticosteroids. Studies in asthma patients have shown that eosinophils co-localise with airway sensory nerves, and after allergen challenge, are associated with neuronal sensitivity. We evaluated whether mepolizumab, a monoclonal antibody targeting interleukin-5, reduces cough in patients with eosinophilic airways disease. METHODS: We conducted a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial of 30 patients with refractory chronic cough and eosinophilic airways disease (sputum eosinophils ≥2%). Patients underwent 1:1 randomisation to receive subcutaneous mepolizumab (100 mg) or placebo every 4 weeks for 12 weeks. Change from baseline in 24-h cough frequency at 14 weeks represented the primary end-point. MEASUREMENTS AND MAIN RESULTS: Compared to placebo, mepolizumab did not lead to improvements in 24-h cough frequency at 14 weeks (percentage change relative to placebo +18.0%, 95% CI -46.4-160.1%; p=0.99). We found no between-group differences in awake cough frequency, sleep cough frequency, cough severity on the 100-mm visual analogue scale, and quality of life on the Leicester Cough Questionnaire. Mepolizumab significantly reduced blood eosinophils compared to placebo at week 14 (mean difference -237.7 cells·µL, 95% CI -328.3--147.1 cells·µL; p<0.0001) and had a significant overall effect in reducing sputum eosinophils over the study (p=0.045). No major adverse events occurred. CONCLUSION: In patients with refractory chronic cough and persistent eosinophilia despite inhaled corticosteroid therapy, mepolizumab did not improve cough despite reducing blood and sputum eosinophils. Targeting eosinophils might not impact cough in these patients, and their cough is probably driven by alternative mechanisms.