Determination of a treatment response threshold for the Eosinophilic Esophagitis Endoscopic Reference Score

Abstract

Background and study aims: While endoscopic features of eosinophilic esophagitis (EoE) are measured using the validated EoE Endoscopic Reference Score (EREFS), a threshold for treatment response has not been defined. We aimed to determine a cut-point for endoscopic response as measured by EREFS. Patients and Methods: We performed a secondary analysis of a randomized clinical trial comparing budesonide slurry to swallowed fluticasone multidose inhaler for initial treatment of EoE. In the parent trial, EREFS was determined before and after treatment (score range 0-9), as were histologic findings and dysphagia symptoms. We performed tabular, flexible trend, and dependent mixture analyses of measures of treatment response to select the best clinical EREFS threshold. Results: In the 111 included subjects (mean age 39 years; 67% male; 96% white), an EREFS threshold of ≤2 was 80% sensitive (95% confidence limits 69 - 88%) and 83% specific (95% confidence limits 67 - 94%) for histologic response (peak of <15 eosinophils per high-power field). Flexible trend analysis and dependent mixture modeling similarly suggested a threshold of ≤2 best captured the correlation of EREFS with histologic and symptomatic measures. Dependent mixture modeling found near total membership in the response class at EREFS of 0 or 1 and >75% at EREFS of 2 or 3. Conclusions: An EREFS of ≤2 was the best clinical threshold for endoscopic response to topical steroid treatment and was consistent with clinical and histologic response. Therefore, future studies can report a binary outcome of endoscopic response when EREFS is two or less.

Posttreatment Gene Scores Support Histologic and Endoscopic Response Thresholds in Eosinophilic Esophagitis

“…There was also a significant difference in EDP scores above and below the 15 eos/hpf histologic threshold. Interestingly, the EREFS data had more variability, which is consistent with previous reports that EREFS modestly correlates with histologic involvement (5,6).…”

“…Similarly, EREFS has been shown to validly measure endoscopic severity and improve (decreasing score) with response to EoE treatment (2,4,5). However, posttreatment EREFS response thresholds have only recently been proposed (6). Furthermore, these posttreatment thresholds have never been assessed in the context of molecular changes in EoE.…”

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions

“…However, despite its value for standardizing reporting of endoscopic severity in both practice and clinical trials, 20,[28][29][30]65,66,94,95 current data do not support using prespecified scores to determine severity. 96 Therefore, a somewhat abbreviated version of the EREFS should be used clinically to assess the endoscopic inflammatory features, defined as edema, furrows, and exudates. In addition, a determination of "localized" vs "diffuse" should be reported.…”

Long-term course of untreated asymptomatic esophageal eosinophilia and minimally symptomatic eosinophilic esophagitis

“…In the diffuse type with no treatment, endoscopic abnormalities persisted but did not exacerbate in most patients without developing symptoms requiring active treatment. In contrast, in the localized type with no treatment, endoscopic activity remained unchanged or rather improved significantly, with a predominance of patients showing endoscopic remission (defined as total EREFS ≤2) in an earlier phase during follow-up [24]. We previously reported that endoscopic abnormalities remained unchanged in the diffuse type but were significantly improved in the localized type of aEE with no treatment for >3 years (median: 50-60 months) [18].…”