Esophagus to Small Intestine
Lancet Gastroenterol Hepatol. 2023;8(5):408−21
1-food versus 6-food elimination diet therapy for the treatment of eosinophilic esophagitis: A multicenter, ran-domized, open-label trial
Background: Empirical elimination diets are effective for achieving histological remission in eosinophilic esophagitis (EoE), but randomized trials comparing diet therapies are lacking. The authors aimed to compare a 6-food elimination diet (6-FED) with a 1-food elimination diet (1-FED) for the treatment of adults with EoE.
Methods: They conducted a multicenter, randomized, open-label trial across 10 sites of the Consortium of Eosinophilic Gastrointestinal Disease Researchers in the USA. Adults aged 18−60 years with active, symptomatic EoE were centrally randomly allocated (1:1; block size of 4) to 1-FED (animal milk) or 6-FED (animal milk, wheat, egg, soy, fish and shellfish, and peanut and tree nuts) for 6 weeks. Randomization was stratified by age, enrolling site, and gender. The primary end point was the proportion of patients with histological remission (peak esophageal count < 15 eosinophils per high-power field [eos/hpf]). Key secondary end points were the proportions with complete histological remission (peak count ≤ 1 eos/hpf) and partial remission (peak counts ≤ 10 and ≤ 6 eos/hpf) and changes from baseline in peak eosinophil count and scores on the Eosino-philic Esophagitis Histology Scoring System (EoEHSS), Eosinophilic Esophagitis Endoscopic Reference Score (EREFS), Eosinophilic Esophagitis Activ-ity Index (EEsAI), and quality of life (Adult Eosinophilic Esophagitis Quality-of-Life and Patient Reported Outcome Measurement Information System Global Health questionnaires). Individuals without histological response to 1-FED could proceed to 6-FED, and those without histological response to 6-FED could proceed to swallowed topical fluticasone propionate 880 μg twice per day (with unrestricted diet), for 6 weeks. Histo-logical remission after switching therapy was assessed as a secondary end point. Efficacy and safety analyses were done in the intention-to-treat (ITT) population.
Findings: Between May 23, 2016, and March 6, 2019, 129 patients (70 men [54%] and 59 women [46%]; mean age 37.0 years [SD 10.3]) were enrolled, randomly assigned to 1-FED (n = 67) or 6-FED (n = 62), and included in the ITT population. At 6 weeks, 25 of 62 patients (40%) in the 6-FED group had histological remission compared with 23 of 67 (34%) in the 1-FED group (difference, 6% [95% confidence interval: -11−23]; p = 0.58). The authors found no significant difference between the groups at stricter thresholds for partial remission (≤ 10 eos/hpf, difference, 7% [-9−24], p = 0.46; ≤ 6 eos/hpf, 14% [-0−29], p = 0.069); the proportion with complete remission was significantly higher in the 6-FED group than in the 1-FED group (difference, 13% [2−25]; p = 0.031). Peak eosinophil counts decreased in both groups (geometric mean ratio = 0.72 [0.43−1.20]; p = 0.21). For 6-FED versus 1-FED, mean changes from baseline in EoEHSS (-0.23 vs. -0.15; difference, -0.08 [-0.21−0.05]; p = 0.23), EREFS (-1.0 vs. -0.6; difference, -0.4 [-1.1−0.3]; p = 0.28), and EEsAI (-8.2 vs. -3.0; difference, -5.2 [-11.2−0.8]; p = 0.091) were not significantly different. Changes in quality-of-life scores were small and similar between the groups. No adverse event was observed in more than 5% of pa-tients in either diet group. For patients without histological response to 1-FED who proceeded to 6-FED, 9 of 21 (43%) reached histological remis-sion; for patients without histological response to 6-FED who proceeded to fluticasone propionate, 9 of 11 (82%) reached histological remission.
Interpretation: Histological remission rates and improvements in histological and endoscopic features were similar after a 1-food elimination diet (1-FED) and a 6-food elimination diet (6-FED) in adults with eosinophilic esophagitis (EoE). 6-FED had efficacy in just less than half of 1-FED non-responders and steroids had efficacy in most 6-FED non-responders. The findings indicate that eliminating animal milk alone is an acceptable initial dietary therapy for EoE.