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

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.

Understanding the GERD.

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.

Use of breath carbon monoxide measurements to assess erythrocyte survival in subjects with chronic diseases.

Anemia is very common in patients with chronic diseases. To determine the role of increased red blood cell (RBC) turnover in such subjects, we estimated RBC survival in three groups of chronically ill patients using a simple technique in which RBC life span is estimated via measurements of breath carbon monoxide concentration. The study groups consisted of subjects with: (1) osteoarthritis, (2) rheumatoid arthritis, and (3) anemia who were hospitalized for treatment of a variety of chronic illnesses. None of the anemic subjects had evidence of hemorrhage, a deficiency state, or a marrow abnormality to account for their reduced hemoglobin concentration. Subjects with osteoarthritis had a mean RBC life span (127 +/- 25 days) that did not differ significantly from normal (122 +/- 23 days). In contrast, RBC life span was significantly reduced (P < 0.001) in both the rheumatoid arthritis subjects (90 +/- 15 days) and the anemic, hospitalized patients (87 +/- 33 days). The hemoglobin concentration of the rheumatoid patients was near normal (13.5 +/- 1.5 g/dl), indicating that the marrow was compensating for the reduced RBC life span, whereas no such compensation was apparent in the anemic, chronically ill subjects. We conclude that a modest (approximately 25%) reduction in RBC life span commonly occurs in patients with chronic disease, and this reduction becomes clinically relevant in subjects whose marrow cannot respond with increased RBC output.

Use of breath carbon monoxide to measure the influence of prosthetic heart valves on erythrocyte survival.

First-generation prosthetic heart valves commonly caused sufficient red blood cell (RBC) injury to induce hemolytic anemia. Although multiple studies have shown that new-generation valves are not associated with anemia, the extent to which these valves are injurious to RBCs is not known, because RBC survival not has not been measured in these subjects. Using a technique that uses breath carbon monoxide (CO) to quantify RBC turnover, this study measured RBC life span in 38 subjects with normally functioning, new-generation valves. Erythrocyte survival averaged 98.8 +/- 23 and 103 +/- 15 days, respectively, in 20 subjects with mechanical valves and 18 subjects with bioprosthetic valves (p >0.05). However, these life spans were significantly (p <0.01) less than those of healthy subjects (122 +/- 23 days) and a group of elderly subjects with osteoarthritis (128 +/- 26 days). The mean hemoglobin concentrations of the 2 groups of valve patients were within normal limits. In conclusion, new-generation heart valves commonly are associated with a small degree of hemolysis that is compensated for by increased RBC production.