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Oral corticosteroids reduce type 2 inflammatory biomarkers and small-airway obstruction in mepolizumab-treated severe eosinophilic asthma patients.

Mepolizumab inhibits IL-5 activity and decreases exacerbation frequency and oral corticosteroid (OCS) maintenance dose in individuals with severe eosinophilic asthma (SEA). Some patients remain dependent on OCS despite use of anti-IL-5 medication, implying persistent corticosteroid-sensitive pathways.

This study, published in The Journal of Allergy and Clinical Immunology, aimed to determine the clinical and anti-inflammatory benefits of OCS in mepolizumab-treated patients with SEA.

The study used a randomized, triple-blind, placebo-controlled crossover design with prednisolone doses of 0.5 mg/kg/d, maximum 40 mg/d, for 14 ± 2 days. Adults with SEA who had received mepolizumab for at least 12 weeks were enrolled. Changes in asthma symptoms, quality of life, lung function determined by spirometry and airwave oscillometry, fractional exhaled nitric oxide, and blood and sputum eosinophil cell count following prednisolone versus placebo treatment were evaluated.

Prednisolone did not improve the 5-item Asthma Control Questionnaire, the mini-Asthma Quality of Life Questionnaire, or the St. George’s Respiratory Questionnaire. The mean difference for forced expiratory volume in one second (FEV1) in favor of prednisolone was 105 ml; forced expiratory flow improvement at 25% and 75% was 484 ml/s (95% CI, 151 to 816 ml/s); fractional exhaled nitric oxide was reduced by 41%; and blood eosinophil count was reduced by 49%.

OCS improved small-airway blockage and decreased biomarkers of type 2 inflammation in SEA patients taking mepolizumab but did not affect symptoms or quality of life.

Following IL-5 suppression with mepolizumab, SEA continues to respond to OCS, although with no further improvements in lung function or reduced frequency of exacerbations; therefore, the therapeutic value of subsequent OCS is unclear. Prednisolone could potentially further reduce inflammation and enhance lung function after therapy with mepolizumab via various mechanisms, including further T2 suppression, effect on mast cell activity, reduction of airway hyperresponsiveness, and greater corticosteroid sensitivity. Improvements in minor airway obstruction were dissociated from additional reductions in T2 inflammation in patients receiving mepolizumab. The study data imply that the clinical efficacy of prednisolone and the corticosteroid responsiveness phenotype should not be presumed after the administration of biological treatment.

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Although corticosteroids will continue to play a role in managing severe asthma, to prevent excessive corticosteroid exposure it is important to differentiate individuals who are responsive to corticosteroids from those who are not.  

Further studies are needed to understand the therapeutic benefits of prednisolone in severe eosinophilic asthma after IL-5 suppression and during exacerbation states.

 

Reference:

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., & Chaudhuri, R. (2022). Corticosteroid Responsiveness Following Mepolizumab in Severe Eosinophilic Asthma-A Randomized, Placebo-Controlled Crossover Trial (MAPLE). J Allergy Clin Immunol Pract, 10(11), 2925-2934.e2912. https://doi.org/10.1016/j.jaip.2022.06.050