Background Mepolizumab and prednisolone have overlapping anti-inflammatory effects so the clinical effects of prednisolone might be attenuated in severe eosinophilic asthma (SEA) patients treated with mepolizumab.

Methods We tested this hypothesis in a randomized, double-blinded, placebo-controlled, crossover trial of prednisolone (0.5 mg/kg/day, 2 weeks) after ≥12 weeks of mepolizumab. Symptoms and quality of life (QoL) questionnaire scores, lung function including oscillometry and markers of inflammation were measured before and after prednisolone and placebo.

Results There were no significant changes in asthma symptoms and QoL questionnaire scores following prednisolone treatment. In comparison to placebo, prednisolone improved FEV₁ by 100 ml (p=0.019) and FEF_25-75 by 200 ml/s (p=0.006). Median FeNO at baseline was 37ppb. Prednisolone reduced FeNO by 13.0ppb (p=0.001), blood eosinophil count by 0.02 × 10⁹/L (p=0.003) and sputum eosinophil percentage of total cell count by 1.4% (p=0.002) in comparison to placebo. Post-prednisolone and post-placebo SNOT-20 questionnaire scores indicated there were no improvements in nasal symptoms following prednisolone in patients on mepolizumab.

Conclusion In patients with severe eosinophilic asthma treated with mepolizumab, prednisolone has no significant effects on symptoms or quality of life but improves FEV₁ and small airway function and reduces FeNO.