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

Freda Yang, John Busby, Liam G. Heaney, I. Pavord, Chris Brightling, K Borg, Pamela Jane McDowell, Sarah E Diver, Rahul Shrimanker, Peter Bradding, Malcolm Shepherd, Rekha Chaudhuri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
24 Downloads (Pure)

Abstract

Background: 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.

Objective: We aimed to determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab.

Methods: 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.

Results: 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 FEV1 in favour of prednisolone was 105ml (95% CI -4 to 213 ml); FEF25-75 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%).
Conclusion: 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.
Original languageEnglish
JournalThe Journal of Allergy and Clinical Immunology: In Practice
Early online date18 Jul 2022
DOIs
Publication statusEarly online date - 18 Jul 2022

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