Corticosteroid responsiveness following mepolizumab in severe eosinophilic asthma—a randomized, placebo-controlled crossover trial (MAPLE)

Yang, F. et al. (2022) Corticosteroid responsiveness following mepolizumab in severe eosinophilic asthma—a randomized, placebo-controlled crossover trial (MAPLE). Journal of Allergy and Clinical Immunology: In Practice, 10(11), 2925-2934.e12. (doi: 10.1016/j.jaip.2022.06.050) (PMID:35863669)

Abstract

Mepolizumab inhibits interleukin-5 (IL-5) activity, reduces exacerbation 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. We aimed to determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab. We conducted a randomised, triple-blind, placebo-controlled crossover trial of prednisolone (0.5mg/kg/day, maximum 40mg/day, for 14±2 days) in adults with SEA after ≥12 weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, FeNO, and blood and sputum eosinophil cell count after prednisolone and placebo. 27 patients completed the study. Prednisolone did not improve ACQ-5 (mean difference in change for prednisolone vs placebo -0.23, 95% CI -0.58 to 0.11), mini-AQLQ (0.03, 95% CI -0.26 to 0.42), SGRQ (0.24, 95% CI -3.20 to 3.69) or VAS scores for overall asthma symptoms (0.11, 95% CI -0.58 to 0.80). The mean difference for FEV in favour of prednisolone was 105ml (95% CI -4 to 213 ml); FEF 484ml/s (95% CI 151 to 816 ml/s); FeNO 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 severe eosinophilic asthma receiving treatment with mepolizumab. [Abstract copyright: Copyright © 2022. Published by Elsevier Inc.]

• Item Type: Articles
• Keywords: Interleukin-5, corticosteroid resistance, mepolizumab, IL-5, Type 2 inflammation, eosinophils, oral corticosteroids, prednisolone, Asthma, severe eosinophilic asthma, T2.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Chaudhuri, Dr Rekha and Yang, Dr Freda and Shepherd, Professor Malcolm
• Authors: Yang, F., Busby, J., Heaney, L. G., Pavord, I. D., Brightling, C. E., Borg, K., McDowell, J. P., Diver, S. E., Shrimanker, R., Bradding, P., Shepherd, M., and Chaudhuri, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Allergy and Clinical Immunology: In Practice
• Publisher: Elsevier
• ISSN: 2213-2198
• ISSN (Online): 2213-2201
• Published Online: 19 July 2022
• Copyright Holders: Copyright © 2022 Crown Copyright
• First Published: First published in The Journal of Allergy and Clinical Immunology: In Practice 10(11): 2925-2934.e12
• Publisher Policy: Reproduced under a Creative Commons License