Mepolizumab
Mepolizumab neutralizes IL-5, through the inactivation of the signaling of IL-5 with the receptor and limiting the proliferation and activation of eosinophils. Mepolizumab is registered for use in adolescents (> 12 years) by the FDA and in children (> 6 years) by the EMA. It is indicated as an add-on maintenance therapy of severe asthma in patients with circulating eosinophils count >150 cells/µL, or >300 cell/µL in the last year, unresponsive to standard treatment, with two or more severe exacerbations every year and/or dependency on systemic corticosteroids.1,2 Several studies confirm its effectiveness and tolerability in these patients. In contrast, no benefit is demonstrated in milder asthma that is not necessarily eosinophilic. Mepolizumab is administered subcutaneously every four weeks at a dose of 40 mg for children, at 100 mg for adolescents and adults. Adverse events include headaches, eczema, and nasal congestion. No case of anaphylaxis is reported. The response to the drug can be assessed at 12 months to determine whether to continue therapy. Long-term use could maintain a stable effect. However, the optimal duration of therapy is unclear. Mepolizumab reduces the number of eosinophils, improving the control of asthma symptoms, and decreasing the hospitalization rate. A Cochrane meta-analysis of mepolizumab vs. placebo in asthma, including 1707 patients aged 12 years and over, shows a reduction of exacerbation rates (of 53% with 95% CI 37-65) and increase in FEV1 from baseline (p=0.03) for ones randomized to subcutaneous mepolizumab. Another study demonstrates a prednisone dose reduction 2.39 times greater with mepolizumab (95% CI 1.25-4.56) compared to placebo.3.
The approval of mepolizumab in children (6–11 years) is based on the effectiveness data gained in the few trials enrolling children, and on the data about adolescents.4 Further researches are still ongoing.
For atopic dermatitis, mepolizumab shows only a modest improvement in clinical so far. Therefore, its application may be tried only in selected refractory patients.5
In the pediatric management of eosinophilic esophagitis, the role of mepolizumab is unclear. A multicenter study treats 59 children with different doses of mepolizumab: the decrease in esophageal eosinophil counts is shown, but there is a limited effect on clinical symptoms.6 Thus, the therapy is off-label and not clearly of benefit at this time.