Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial

Abstract

Objective: We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE).

Methods: We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6).

Results: Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions.

Conclusions: Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement.

Trial registration number: NCT03656380.

Keywords: CLINICAL TRIALS; DYSPHAGIA; HISTOPATHOLOGY; OESOPHAGEAL DISEASE.

Figure 1.

Primary and key secondary study outcomes at month 3. (A) Change in dysphagia symptoms as measured by the EEsAI score from baseline to month 3 in the placebo (black bar) and mepolizumab (gray bar) groups. (B) Change in the absolute peak esophageal eosinophil count (eos/hpf) from baseline to month 3. (C) Proportion of subjects with histologic response at month 3 at the <15 eos/hpf (black bars), ≤6 eos/hpf (medium gray bars), and <1 eos/hpf (light gray bars) levels. (D) Change in endoscopic severity as measured by EREFS from baseline to month 3.

Figure 2.

Symptom scores (± standard deviations) over the study timeframe for mepolizumab (gray solid line) and placebo (black dotted line). (A) Monthly EEsAI scores. (B) Weekly SDI scores.