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Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomized, placebo-controlled, double-blind trial
  1. Alex Straumann1,
  2. Sebastien Conus2,
  3. Pascale Grzonka2,
  4. Hirohito Kita3,
  5. Gail Kephart3,
  6. Christian Bussmann4,
  7. Christoph Beglinger5,
  8. Deborah Smith6,
  9. Jatin Patel6,
  10. Margaret Byrne6,
  11. Hans-Uwe Simon2,*
  1. 1 Gastroenterology Olten, Switzerland;
  2. 2 University of Bern, Switzerland;
  3. 3 Mayo Clinic Rochester, Switzerland;
  4. 4 Clinical Pathology Basel, United States;
  5. 5 University of Basel, United States;
  6. 6 GSK, Switzerland
  1. Correspondence to: Hans-Uwe Simon, UNIVERSITY OF BERN, Department of Pharmacology, University of Bern, 3010 Bern, SWITZERLAND; hus{at}


Objective: Eosinophilic oesophagitis (EoE) is a clinico-pathological condition defined by proton-pump-inhibitor refractory oesophageal symptoms combined with oesophageal eosinophilia. We evaluated the pharmacodynamic effect of mepolizumab (a humanized anti-interleukin-5 monoclonal antibody) in EoE.

Methods: Eleven adults with active EoE (>20 peak eosinophil number/hpf and dysphagia) were randomized to 750 mg mepolizumab (n=5) or placebo (n=6) and received two intravenous infusions, one week apart. Those not in complete remission (<5 peak eosinophil number/hpf) after 8 weeks received two further doses four weeks apart, 1500 mg 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%) four 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 TGF-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 therapy. Mepolizumab was well tolerated.

Conclusions: Mepolizumab significantly reduced eosinophil numbers in oesophageal tissues in adult patients with active EoE and changes in the expression of molecules associated with oesophageal remodeling were reversed. Minimal clinical improvement was achieved in a subgroup of EoE patients. Mepolizumab had an acceptable safety profile, even at the high 1500 mg dose level.

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