Because the effect of mepolizumab on the eosinophilic oesophagitis (EoE) Histologic Scoring System (HSS) is unknown, we performed a secondary analysis of a clinical trial (NCT03656380) of mepolizumab 300 mg subcutaneously monthly versus placebo to comprehensively analyse HSS grade and stage scores. Mepolizumab had significantly lower HSS vs. placebo for both grade (0.39 ± 0.14 vs. 0.56 ± 0.21; p < 0.001) and stage (0.37 ± 0.14 vs. 0.53 ± 0.20; p < 0.001). HSS correlated with endoscopic severity for grade (R = 0.45, p < 0.001) and stage (R = 0.47, p < 0.001), but improvement was primarily limited to the eosinophil-dependent HSS features. Eosinophil-focused treatments alone may not provide comprehensive treatment response across multiple outcome domains in EoE.

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.

Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disorder in the United States. Without proper treatment, patients may be at risk for long-term complications including Barrett's esophagus and adenocarcinoma of the esophagus. Because reflux is a common complaint, clinicians need to know how to rule out causes other than GERD and how to treat patients suspected of having GERD. This article discusses how to diagnose GERD, the medical and surgical treatment options, and how to evaluate patients who are at risk for long-term complications.