OBJECTIVE: Eosinophilic oesophagitis (EoO) is a clinicopathological condition 
defined by proton pump inhibitor-refractory oesophageal symptoms combined with 
oesophageal eosinophilia. The pharmacodynamic effect of mepolizumab (a humanised 
anti-interleukin-5 monoclonal antibody) in EoO was evaluated.
METHODS: Eleven adults with active EoO (>20 peak eosinophil number/high power 
field (hpf) and dysphagia) were randomised to 750 mg of mepolizumab (n = 5) or 
placebo (n = 6) and received two intravenous infusions, 1 week apart. Those not 
in complete remission (<5 peak eosinophil number/hpf) after 8 weeks received two 
further doses 4 weeks apart, 1500 mg of mepolizumab or placebo. The effect of 
mepolizumab was assessed clinically, endoscopically, histologically, and via 
blood and tissue biomarkers.
RESULTS: As assessed by immunofluorescence, a marked reduction of mean 
oesophageal eosinophilia (p = 0.03) was seen in the mepolizumab group (-54%) 
compared with the placebo group (-5%) 4 weeks after initiation of treatment. No 
further reduction of eosinophil numbers was observed in response to the two 
additional infusions in either group. Mepolizumab reduced tenascin C (p = 0.033) 
and transforming growth factor beta1 (p = 0.05) expression in the oesophageal 
epithelial layer 13 weeks after initiation of treatment. Clinically, limited 
improvement of symptoms was seen, although a trend was seen between 4 and 13 
weeks after initiation of mepolizumab treatment. Mepolizumab was well tolerated.
CONCLUSIONS: Mepolizumab significantly reduced eosinophil numbers in oesophageal 
tissues in adult patients with active EoO, and changes in the expression of 
molecules associated with oesophageal remodelling were reversed. Minimal 
clinical improvement was achieved in a subgroup of patients with EoO. 
Mepolizumab had an acceptable safety profile, even at the high 1500 mg dose 
level.
TRIAL REGISTRATION NUMBER: NCT00274703.