Abstract
Background: Empirical elimination diets are effective for achieving histological remission in eosinophilic oesophagitis, but randomised trials comparing diet therapies are lacking. We aimed to compare a six-food elimination diet (6FED) with a one-food elimination diet (1FED) for the treatment of adults with eosinophilic oesophagitis. Methods: We conducted a multicentre, randomised, open-label trial across ten sites of the Consortium of Eosinophilic Gastrointestinal Disease Researchers in the USA. Adults aged 18–60 years with active, symptomatic eosinophilic oesophagitis were centrally randomly allocated (1:1; block size of four) to 1FED (animal milk) or 6FED (animal milk, wheat, egg, soy, fish and shellfish, and peanut and tree nuts) for 6 weeks. Randomisation was stratified by age, enrolling site, and gender. The primary endpoint was the proportion of patients with histological remission (peak oesophageal count <15 eosinophils per high-power field [eos/hpf]). Key secondary endpoints 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 Eosinophilic Esophagitis Histology Scoring System (EoEHSS), Eosinophilic Esophagitis Endoscopic Reference Score (EREFS), Eosinophilic Esophagitis Activity 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 1FED could proceed to 6FED, and those without histological response to 6FED could proceed to swallowed topical fluticasone propionate 880 μg twice per day (with unrestricted diet), for 6 weeks. Histological remission after switching therapy was assessed as a secondary endpoint. Efficacy and safety analyses were done in the intention-to-treat (ITT) population. This trial is registered on ClinicalTrials.gov, NCT02778867, and is completed. Findings: Between May 23, 2016, and March 6, 2019, 129 patients (70 [54%] men and 59 [46%] women; mean age 37·0 years [SD 10·3]) were enrolled, randomly assigned to 1FED (n=67) or 6FED (n=62), and included in the ITT population. At 6 weeks, 25 (40%) of 62 patients in the 6FED group had histological remission compared with 23 (34%) of 67 in the 1FED group (difference 6% [95% CI –11 to 23]; p=0·58). We found no significant difference between the groups at stricter thresholds for partial remission (≤10 eos/hpf, difference 7% [–9 to 24], p=0·46; ≤6 eos/hpf, 14% [–0 to 29], p=0·069); the proportion with complete remission was significantly higher in the 6FED group than in the 1FED group (difference 13% [2 to 25]; p=0·031). Peak eosinophil counts decreased in both groups (geometric mean ratio 0·72 [0·43 to 1·20]; p=0·21). For 6FED versus 1FED, mean changes from baseline in EoEHSS (–0·23 vs –0·15; difference –0·08 [–0·21 to 0·05]; p=0·23), EREFS (–1·0 vs –0·6; difference –0·4 [–1·1 to 0·3]; p=0·28), and EEsAI (–8·2 vs –3·0; difference –5·2 [–11·2 to 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 patients in either diet group. For patients without histological response to 1FED who proceeded to 6FED, nine (43%) of 21 reached histological remission; for patients without histological response to 6FED who proceeded to fluticasone propionate, nine (82%) of 11 reached histological remission. Interpretation: Histological remission rates and improvements in histological and endoscopic features were similar after 1FED and 6FED in adults with eosinophilic oesophagitis. 6FED had efficacy in just less than half of 1FED non-responders and steroids had efficacy in most 6FED non-responders. Our findings indicate that eliminating animal milk alone is an acceptable initial dietary therapy for eosinophilic oesophagitis. Funding: US National Institutes of Health.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 408-421 |
| Number of pages | 14 |
| Journal | The Lancet Gastroenterology and Hepatology |
| Volume | 8 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2023 |
Funding
This study was fully supported by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR; NIH grant U54 AI117804), which is part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, and is cofounded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Center for Advancing Translational Sciences. CEGIR is also supported by patient advocacy groups including the APFED, CURED Foundation, and Eosinophilic Family Coalition. As a member of the Rare Diseases Clinical Research Network, CEGIR is also supported by its Data Management and Coordinating Center (grant number U2CTR002818). ImmunoCAP tests and the Phadia 100 instrument, manufactured by Thermo Fisher Scientific, were provided by Phadia US (Portage, MI, USA). ESD, DAK, JPA, SSA, MC, GWF, SKG, PM-K, JL, IH, VAM, GTF, and MER received support from the NIH grant U54 AI117804. ESD has received research support from NIH R01 grants (ES031940, DK132001, and AI139126), and an NIH R21 grant (DK122297); SSA from NIAID and NIDDK R01 grants; MC from NIH R01 grants (AI140133 and ES031940); KAP from an NIH R21 grant (AI139438-02); MER from an NIH U19 grant (AI070235), R01 grants (AI045898, Al148138, and AI24355); and TS from an NIH K99/R00 grant (Al58660). AKRS was employed by the NIH at the time of the study. AKRS's co-authorship of this publication does not necessarily constitute endorsement by the NIAID, the NIH, or any other agency of the US Government. The authors would like to thank Madelynn Strong, Bethany Doerfler, Cynthia Knott, Ruth Tanner-Schramm, and the other CEGIR dietitians who supported the study. This study was fully supported by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR; NIH grant U54 AI117804), which is part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, and is cofounded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Center for Advancing Translational Sciences. CEGIR is also supported by patient advocacy groups including the APFED, CURED Foundation, and Eosinophilic Family Coalition. As a member of the Rare Diseases Clinical Research Network, CEGIR is also supported by its Data Management and Coordinating Center (grant number U2CTR002818). ImmunoCAP tests and the Phadia 100 instrument, manufactured by Thermo Fisher Scientific, were provided by Phadia US (Portage, MI, USA). ESD, DAK, JPA, SSA, MC, GWF, SKG, PM-K, JL, IH, VAM, GTF, and MER received support from the NIH grant U54 AI117804. ESD has received research support from NIH R01 grants (ES031940, DK132001, and AI139126), and an NIH R21 grant (DK122297); SSA from NIAID and NIDDK R01 grants; MC from NIH R01 grants (AI140133 and ES031940); KAP from an NIH R21 grant (AI139438-02); MER from an NIH U19 grant (AI070235), R01 grants (AI045898, Al148138, and AI24355); and TS from an NIH K99/R00 grant (Al58660). AKRS was employed by the NIH at the time of the study. AKRS's co-authorship of this publication does not necessarily constitute endorsement by the NIAID, the NIH, or any other agency of the US Government. The authors would like to thank Madelynn Strong, Bethany Doerfler, Cynthia Knott, Ruth Tanner-Schramm, and the other CEGIR dietitians who supported the study.
ASJC Scopus subject areas
- Hepatology
- Gastroenterology