Hirano, Ikuo

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended to encourage question-asking by patients and enhance patient-physician communication. To date, an EoE-specific QPL has not been developed for EoE patients. Aim: To develop a preliminary QPL specific to adults with EoE by incorporating input from international esophageal experts. Methods: Sixteen experts were invited to generate QPL content through a modified Delphi (RAND/University of California, Los Angeles, CA) method consisting of 2 rounds of independent ratings. In round 1, experts provided 5 answers to the prompts “what general questions should patients ask when being seen for EoE?” and “what questions do I not hear patients asking but given my experience, I believe they should be asking?” In round 2, experts rated each question on a 5-point Likert scale, and responses rated as “essential” or “important” (determined by an a priori median threshold of ≥ 4.0) were accepted for the EoE QPL. Results: Ten esophageal experts participated in both rounds. Round 1 generated 100 questions. Questions were combined and modified to reduce redundancy, yielding 57 questions. After round 2, 51 questions (85%) were accepted for inclusion (median value ≥ 4.0) in the final QPL. Questions were then divided into 4 themes based on disease domains: (1) “What is EoE?,” (2) “Treatment Options,” (3) “Follow-up Surveillance and Long-term Risks,” and (4) “Allergy and Genetic Testing.” The largest number of questions covered was “What is EoE?” (16/51 or 31%). Questions with the highest agreement median (5.0) included examples such as “what should I do if I get a food impaction?” and “what are the treatment options?” Conclusion: This is the first preliminary EoE QPL developed in the field of medicine. We hope implementation enhances effective patient-physician communication by encouraging patients to ask relevant questions that experts prioritized. Future studies will aim to modify this communication tool by incorporating patient perspectives

Summary Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists. Questions focused on management of patients from presentation to post-endoscopy follow-up. The survey was administered to a list of eligible candidates provided by societies of gastroenterology. A total of 308 endoscopists completed the questionnaire. The majority (83%) practiced in Europe and treated adults (78%). Most agreed patients should be advised to seek emergency care (66%) within 1 to 2 hours (41% agreement). There was agreement that medications to induce vomiting should be avoided (84%) and that blood tests or imaging studies were usually not required before endoscopy. By contrast, there was more variability in the type of sedation recommended and the need for endotracheal intubation, especially when comparing more experienced with less experienced EoE-endoscopists. Overall, fewer than half (43%) respondents recommended obtaining esophageal biopsies during the initial endoscopy. However, there were significant differences in the proportion who recommended biopsies based on level of EoE-experience (25, 52, 77%, P < 0.001; less vs. moderate vs. very experienced) and comparing pediatric and adult endoscopists (32, vs. 79%, P < 0.001; adult vs. pediatric). There exists heterogeneity among endoscopists in recommendations to manage EFI in patients with EoE. These findings support development of clinical guidelines and new studies to clarify the rationale for best practices. Key summary: Established knowledge—The optimal management of patients with esophageal food impaction due to eosinophilic esophagitis from presentation at the emergency department to postendoscopy care is unclear. New findings—Considerable recommendation variation exists in the management of EFI in patients with EoE. Our findings provide a rationale for the creation of consensus practice guidelines and further study into best practices.

INTRODUCTION: Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach characterized by eosinophil-predominant gastric mucosal inflammation and gastrointestinal symptoms. The aim of this study was to prospectively evaluate endoscopic features in a large series of children and adults with EG to better understand the endoscopic manifestations and develop a standardized instrument for investigations. METHODS: Data were prospectively collected as part of the Consortium for Eosinophilic Gastrointestinal Disease Researchers, a national collaborative network. Endoscopic features were prospectively recorded using a system specifically developed for EG, the EG Endoscopic Reference System (EG-REFS). Correlations were made between EG-REFS and clinical and histologic features. RESULTS: Of 98 patients with EG, 65 underwent assessments using EG-REFS. The most common findings were erythema (72%), raised lesions (49%), erosions (46%), and granularity (35%); only 8% of patients with active histology (≥30 eosinophils/high-power field) exhibited no endoscopic findings. A strong correlation between EG-REFS scores and physician global assessment of endoscopy severity was demonstrated (Spearman r = 0.84, P < 0.0001). The overall score and specific components of EG-REFS were more common in the antrum than in the fundus or body. EG-REFS severity was significantly correlated with active histology, defined by a threshold of ≥30 eosinophils/high-power field ( P = 0.0002). DISCUSSION: Prospective application of EG-REFS identified gastric features with a strong correlation with physician global assessment of endoscopic activity in EG. Endoscopic features demonstrated greater severity in patients with active histology and a predilection for the gastric antrum. Further development of EG-REFS should improve its utility in clinical studies.

INTRODUCTION: The optimal instrument for assessing histologic disease activity in patients with eosinophilic esophagitis (EoE) is unclear. We assessed the responsiveness of the EoE Histologic Scoring System (EoE-HSS) when compared with that of the peak eosinophil count (PEC). METHODS: Histopathology slides were obtained from patients with EoE at baseline and after 8 weeks of treatment with swallowed topical budesonide or elimination diet. Two blinded gastrointestinal pathologists scored biopsies on the EoE-HSS, PEC, and 100-mm visual analog scale (VAS) of overall histologic severity. Change was defined as an improvement by ≥0.5 SD in baseline VAS. Responsiveness was quantified using the standardized effect size (SES) and the probability that the index distinguishes a patient with improvement from a patient without improvement, which is the area under the receiver operating characteristic curve (AUC). Longitudinal validity was assessed using Pearson correlations between changes in EoE-HSS and both PEC and VAS. RESULTS: The EoE-HSS grade (SES 2.18 [95% confidence interval, CI: 1.46–2.88]; AUC 0.73 [95% CI: 0.57–0.84]) and stage (SES 2.07 [95% CI: 1.37–2.77]; AUC 0.73 [95% CI: 0.58–0.84]) were highly responsive, similar to PEC (SES 1.44 [95% CI: 0.80–2.07]; AUC 0.73 [95% CI: 0.58–0.84]). The EoE-HSS grade and stage were more highly correlated with changes in VAS (grade 0.92 [95% CI: 0.86–0.95]; stage 0.89 [95% CI: 0.81–0.94]) than with changes in PEC (grade 0.74 [95% CI: 0.58–0.85]; stage 0.66 [95% CI: 0.47–0.80]). DISCUSSION: The EoE-HSS is highly responsive, performs similarly to PEC, and is better correlated with changes in overall histologic activity in patients with EoE.

Abstract Eosinophilic esophagitis (EoE), gastritis (EG), and/or duodenitis (EoD) are associated with accumulation and activation of eosinophils and mast cells in the esophagus, stomach, and/or duodenum, respectively. Lirentelimab (AK002), an antibody against siglec-8, depletes eosinophils and inhibits mast cells. We performed an open-label extension (OLE) study of subjects who completed ENIGMA (a randomized, double-blind, placebo-controlled phase 2 study of lirentelimab in adults with symptomatic, biopsy-confirmed EG and/or EoD, with or without EoE) to evaluate long-term responses. Methods Subjects who received 4 monthly infusions of lirentelimab or placebo during ENIGMA (n = 59) were eligible for the OLE; they received monthly, escalating doses of lirentelimab (0.3 or 1 mg/kg escalating to 3 mg/kg). Symptoms were assessed weekly using an electronic daily patient-reported outcome questionnaire and total symptom scores (TSS) were calculated. Patients underwent upper endoscopy with biopsy at screening and at the end of ENIGMA (day 99, week 16, blinded); in the OLE, endoscopies were performed on day 323 (30 weeks after the first dose in the OLE). Histopathology was assessed by a single pathologist. Results Fifty-eight subjects entered the OLE; 45 completed ≥52 weeks lirentelimab (including exposure during ENIGMA) and 29 completed 70 weeks. Mean TSS improved through week 70 (Figure 1). Subjects receiving 70 weeks lirentelimab (ENIGMA+OLE) had further improvements in TSS from baseline (mean reductions: 68% at weeks 29–30, 70% at weeks 51–52, 75% at weeks 69–70). Symptom scores (abdominal pain, nausea, vomiting, early satiety, appetite loss, abdominal cramping, bloating, diarrhea) decreased significantly from baseline. Treatment response was not associated with concomitant EoE. The most common adverse event was mild to moderate infusion-related reactions, usually with the first infusion. Conclusion In the OLE of the ENIGMA study, patients with EG and or EoD (with or without concomitant EoE) who received lirentelimab had sustained tissue eosinophil depletion and significant long-term symptom improvement. Symptoms continued to improve with duration of treatment. Lirentelimab appears to be a promising targeted treatment for EG and/or EoD.