Jackson D, Bacharier L, Gergen P, Gagalis L, Villarreal M, Gill M, Liu A, Gruchalla R, Cohen R, Makhija M, Hershey GK, Sherenian M, Rivera-Spoljaric K, Stokes J, Zoratti E, Teach S, Kattan M, Visness C, Becker P, Gern J, Sorkness C, Busse W, and Altman M. Phenotype-directed Therapy with Mepolizumab for Urban Children with Exacerbation-Prone Asthma. J Allergy Clin Immunol 2022; 149(2):AB146.
J Allergy Clin Immunol
Rationale: Asthma exacerbations are common in urban children and have significant short- and long-term consequences. Elevated peripheral blood and airway eosinophils have been identified as risk factors for exacerbations, and therapies targeting these biomarkers reduce exacerbations in adults; however, data on anti-eosinophil treatment in children and adolescents are limited. The primary objective of this study is to determine if phenotype-directed use of mepolizumab reduces the rate of asthma exacerbations in urban children.
Methods: Urban children 6-17 years of age (n=290) with exacerbation-prone asthma (2+ exacerbations in previous year) and blood eosinophils ≥150/mm3 were randomized 1:1 to mepolizumab (6-11 years: 40 mg; 12-17 years: 100 mg) or placebo every 4 weeks added to guideline-based care for 1 year. The primary outcome was the number of asthma exacerbations treated with systemic corticosteroids; a comparison of the two treatment groups was evaluated using a negative-binomial model.
Results: Mepolizumab significantly reduced peripheral blood eosinophils (p<0.01) and nasal eosinophils (p<0.01). The rate of asthma exacerbations was significantly lower in mepolizumab (0.96 exacerbations/year) vs. placebo (1.30 exacerbations/year) treated participants [relative risk 0.73 (95% confidence interval 0.56-0.96), p=0.027]. There were no significant differences in secondary outcomes, including time to first exacerbation, lung function, quality of life, or composite asthma severity index (CASI). Post hoc, the time to second asthma exacerbation increased significantly with mepolizumab (p=0.02). Adverse events were similar between groups.
Conclusions: Phenotype-directed therapy with mepolizumab in urban children and adolescents with exacerbation-prone eosinophilic asthma significantly reduced recurrent exacerbations and was well tolerated, but did not impact other asthma outcomes.