Severe Pediatric Asthma Therapy: Mepolizumab

Abstract

There is a growing need for advanced treatment in children with persistent and severe asthma symptoms. As a matter of fact, between 2 and 5% of asthmatic children experience repeated hospitalizations and poor quality of life despite optimized treatment with inhaled glucocorticoid plus a second controller. In this scenario, mepolizumab, a humanized monoclonal antibody, has proven to be effective in controlling eosinophil proliferation by targeting interleukin-5 (IL-5), a key mediator of eosinophil activation pathways. Mepolizumab is approved since 2015 for adults at a monthly dose of 100 mg subcutaneously and it has been approved for patients ≥ 6 years of age in 2019. Especially in children aged 6 to 11 years, mepolizumab showed a greater bioavailability, with comparable pharmacodynamics parameters as in the adult population. The recommended dose of 40 mg every 4 weeks for children aged 6 through 11 years, and 100 mg for patients ≥ 12 years provides appropriate concentration and proved similar therapeutic effects as in the adult study group. A marked reduction in eosinophil counts clinically reflects a significant improvement in asthma control as demonstrated by validated questionnaires, reduction of exacerbation rates, and the number of hospitalizations. Finally, mepolizumab provides a safety and tolerability profile similar to that observed in adults with adverse events mostly of mild or moderate severity. The most common adverse events were headache and injection-site reaction. In conclusion, mepolizumab can be considered a safe and targeted step-up therapy for severe asthma with an eosinophilic phenotype in children and adolescents.

Severe asthma guidelines in children and adolescents: A practical document for physicians

“…Many studies prove the efficacy (reduction of exacerbation rate and hospital admission, steroids sparing effect) and safety (lower risk of severe adverse events) of anti-IL5 therapy in patients with severe asthma. 17 Like suggested by 2020 ERS/ATS, the CTS position statement advises against the use of anti-IL5 in pediatrics patients and suggests them as add on treatment in adults with eosinophilic severe uncontrolled asthma (SUA) and those with steroids dependency. 16 While the ERS/ATS Task Force does not suggest the use of anti-IL5 in children and adolescents due to the limited number of treated patients in this age group, 13 the ALAT guideline recommends the prescription of anti-IL5 antibodies (mepolizumab and reslizumab) in patients aged >12 years because the studies included in the analysis reported the reduction of asthma exacerbations rate and the lowering of blood and sputum eosinophils count.…”

“…Many studies prove the efficacy (reduction of exacerbation rate and hospital admission, steroids sparing effect) and safety (lower risk of severe adverse events) of anti‐IL5 therapy in patients with severe asthma 17 …”

Pediatric pulmonology 2022 year in review: Asthma

“…Ullmann et al 11 The authors found that dupilumab was associated with higher costs per patient over a 6 year period ($379 USD per patient per exacerbation for dupilumab compared to $19 USD per patient for standard treatment). 12 These results were similar to other economic analyses performed on adolescents and adults with asthma in Colombia.…”

Molecular targets for cystic fibrosis and therapeutic potential of monoclonal antibodies

“…The antibody exhibited a beneficial effect on type 2 inflammatory markers, decreasing allergic inflammation markers in all CF patients ( Zhang et al, 2020 ). Recently, the outcome of clinical trials showed that mepolizumab is a safe and focused step-up therapy for children and adolescents with severe asthma with an eosinophilic phenotype ( Ullmann et al, 2022 ).…”