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.