An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis

AH Assa'ad, SK Gupta, MH Collins, M Thomson… - Gastroenterology, 2011 - Elsevier
AH Assa'ad, SK Gupta, MH Collins, M Thomson, AT Heath, DA Smith, TL Perschy…
Gastroenterology, 2011Elsevier
BACKGROUND & AIMS: The role of interleukin (IL)-5 in the pathogenesis of eosinophilic
esophagitis (EoE) has been established in animal models; anti–IL-5 therapy has been
reported to be effective in adults. We investigated whether IL-5 has a role in accumulation of
esophageal eosinophils in children with EoE and whether therapy with mepolizumab, an
antibody against IL-5, reduces the number of esophageal intraepithelial eosinophils in
children with EoE. METHODS: We performed an international, multicenter, double-blind …
BACKGROUND & AIMS
The role of interleukin (IL)-5 in the pathogenesis of eosinophilic esophagitis (EoE) has been established in animal models; anti–IL-5 therapy has been reported to be effective in adults. We investigated whether IL-5 has a role in accumulation of esophageal eosinophils in children with EoE and whether therapy with mepolizumab, an antibody against IL-5, reduces the number of esophageal intraepithelial eosinophils in children with EoE.
METHODS
We performed an international, multicenter, double-blind, randomized, prospective study of 59 children with EoE, defined as baseline peak count of esophageal intraepithelial eosinophils of ≥20 in at least 1 high-power field (hpf). Patients received an infusion every 4 weeks (a total of 3 infusions) of 0.55, 2.5, or 10 mg/kg mepolizumab. No placebo group was used.
RESULTS
Baseline peak and mean esophageal intraepithelial eosinophil counts were (mean ± SE) 122.5 ± 8.78 and 39.1 ± 3.63 per hpf, respectively. Four weeks after the third infusion, peak eosinophil counts were <5 per hpf in 5 of 57 children (8.8%); we did not observe differences among groups given different doses of mepolizumab. Reduced peak and mean eosinophil counts, to <20 per hpf, were observed in 18 of 57 (31.6%) and 51 of 57 (89.5%) children, respectively. Peak and mean esophageal intraepithelial eosinophil counts decreased significantly to 40.2 ± 5.17 and 9.3 ± 1.25 per hpf, respectively (P < .0001). An analysis to evaluate predictors of response associated a higher mean baseline esophageal intraepithelial eosinophil count with a greater reduction in mean count (P < .0001).
CONCLUSIONS
IL-5 is involved in the pathogenesis of EoE in children. Mepolizumab, an antibody against IL-5, reduces esophageal eosinophilic inflammation in these patients.
Elsevier