Corticosteroid Responsiveness Following Mepolizumab in Severe Eosinophilic Asthma—A Randomized, Placebo-Controlled Crossover Trial (MAPLE)

Abstract

Mepolizumab inhibits IL-5 activity and reducesexacerbation frequency and maintenance oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma(SEA). Some patients remain dependent on OCS despite anti-IL-5 treatment, suggesting residual corticosteroid-responsive mechanisms. To determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab. We conducted a randomized, triple-blind, placebo-controlled crossover trial of prednisolone (0.5 mg/kg/d, maximum 40 mg/d, for 14 ± 2 days) in adults with SEA after 12 or more weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, fractional exhaled nitric oxide, and blood and sputum eosinophil cell count after prednisolone and placebo treatment. A total of 27 patients completed the study. Prednisolone did not improve 5-item Asthma Control Questionnaire (mean difference in change for prednisolone vs placebo,-0.23; 95% CI,-0.58 to 0.11), mini-Asthma Quality of Life Questionnaire (0.03; 95% CI,-0.26 to 0.42), St. George's Respiratory Questionnaire (0.24; 95% CI,-3.20 to 3.69), or Visual Analogue Scale scores for overall asthma symptoms (0.11; 95% CI,-0.58 to 0.80). The mean difference for FEV1 in favor of prednisolone was 105 mL (95% CI,-4 to 213 mL); forced expiratory flow at 25% and 75% 484 mL/s (95% CI, 151 to 816 mL/s); fractional exhaled nitric oxide reduction 41% (95% CI, 25% to 54%); blood eosinophil count reduction 49% (95% CI, 31% to 62%); and percentage of sputum eosinophil reduction 71% (95% CI, 26% to 89%). OCS improved small-airway obstruction and reduced biomarkers of type 2 inflammation but had no significant effect on symptoms or quality of life in patients with SEA receiving treatment with mepolizumab.