Eosinophilic Esophagitis: Relationship of Subepithelial Eosinophilic Inflammation With Epithelial Histology, Endoscopy, Blood Eosinophils, and Symptoms

Schoepfer, Alain; Simko, A; Bussmann, Christian; Safroneeva, Ekaterina; Zwahlen, Marcel; Greuter, Thomas; Biedermann, Luc; Vavricka, Stephan R.; Godat, Sébastien; Reinhard, Antoine; Saner, Catherine; Maye, Hugo; Sempoux, Christine; Brunel, Christophe; Blanchard, Carine; Simon, Dagmar; Simon, Hans‐Uwe; Straumann, Alex

doi:10.1038/ajg.2017.493

Cited by 37 publications

(22 citation statements)

References 31 publications

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“…The relationship between symptoms in EoE and endoscopic and/or histologic activity is weak . In one third of adult EoE patients in clinical remission, there is ongoing endoscopic and/or histologic activity .…”

Section: Key Points Of Updated International Guidelines 2017mentioning

confidence: 99%

“…The relationship between symptoms in EoE and endoscopic and/or histologic activity is weak. 17 In one third of adult EoE patients in clinical remission, there is ongoing endoscopic and/or histologic activity. 18 Ongoing biologic activity is associated with esophageal remodeling and consecutive stricture formation which represent the main risk factors for long-lasting food bolus impactions that necessitate endoscopic removal.…”

Section: Noninvasive and Semi-invasive Tools To Monitor Eoementioning

confidence: 99%

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Eosinophilic esophagitis: latest insights from diagnosis to therapy

Schoepfer

Blanchard

Dawson

et al. 2018

Annals of the New York Academy of Sciences

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Eosinophilic esophagitis (EoE) represents a chronic, local immune-mediated esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Other systemic and local causes of esophageal eosinophilia should be excluded. Clinical manifestations or pathologic data should not be interpreted in isolation. EoE was first described as a distinct disease entity in 1993. Most patients are diagnosed with underlying food allergies. The first diagnostic and therapeutic guidelines were published in 2007 with a first update in 2011. In 2017, new international guidelines were published based on the GRADE methodology. These guidelines provide, among many other topics, insights on the role of proton pump inhibitor-responsive esophageal eosinophilia. Over the last two decades, considerable progress was made by stakeholders regarding the understanding of EoE's pathogenesis, genetic background, natural history, allergy workup, standardization of assessment of disease activity, evaluation of minimally invasive diagnostic tools, and new therapeutic approaches. This brief review provides further insights into latest diagnostic and therapeutic advances.

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Section: Key Points Of Updated International Guidelines 2017mentioning

confidence: 99%

Section: Noninvasive and Semi-invasive Tools To Monitor Eoementioning

confidence: 99%

Eosinophilic esophagitis: latest insights from diagnosis to therapy

Schoepfer

Blanchard

Dawson

et al. 2018

Annals of the New York Academy of Sciences

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“…Increasing data support transmural inflammatory activity and remodeling consequences of EoE. 8,25 Systemically active therapeutics offer conceptual advantages over topical steroids that target the epithelium. 8,26,27 Finally, although yet unproven, the proposed benefits of IL13 blockade in terms of remodeling aspects of disease may prevent disease progression and disease complications, including esophageal strictures and food impactions.…”

Section: Discussionmentioning

confidence: 99%

RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis

et al. 2019

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Primary Outcome Esophageal eosinophil count: P < .0001 for both dose groups Key Secondary Outcome Dysphagia clinical symptom frequency and severity (DSD): Not statistically significant for both dose groups Safety Assessment AEs All low frequency Headache Upper respiratory tract infection Arthralgia Nasopharyngitis Diarrhea Nausea SAEs All unrelated to treatment RPC4046 180 mg or 360 mg treatment for 16 weeks See editorial on page 545. BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE. METHODS: We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation. RESULTS: At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P ¼ .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P ¼ .0733). Significant reductions in esophageal

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“…Large capacity forceps demonstrated subepithelial sampling in 55% compared to 90% for a specialized, ''static jaw''' type forceps. The high yield of the asymmetric forceps' design was confirmed in a second retrospective study of 200 adults where subepithelial tissue was evaluable in 87% [9]. In this same study, esophageal epithelial eosinophil density only modestly correlated with subepithelial eosinophilic inflammation (rho 0.33).…”

Section: Clinical Methods To Assess Esophageal Subepithelial Disease mentioning

confidence: 71%

Clinical relevance of esophageal subepithelial activity in eosinophilic esophagitis

Hirano

2019

J Gastroenterol

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Esophageal subepithelial activity (ESEA) is an important determinant of disease severity and complications in eosinophilic esophagitis (EoE). Inflammation and fibrosis of the lamina propria and muscularis propria result in esophageal dysfunction and stricture formation that are clinically manifest by symptoms of dysphagia and food impaction as well as the need for esophageal dilation. Esophageal biopsies that are limited to the evaluation of the esophageal epithelium are an inadequate means to assess overall, clinical disease severity in EoE. Instruments for the assessment of subepithelial activity in EoE are both limited and/or underutilized and thus represent an important unmet clinical need. Studies using endoscopic features, endoscopic ultrasonography, and barium esophagography have demonstrated improvement in ESEA parameters with topical steroid therapy. Impedance planimetry is being evaluated as an objective and quantifiable measure of esophageal distensibility that is a consequence of ESEA. In conjunction with symptom and histologic assessment, evaluation of ESEA provides a more complete evaluation of disease activity in EoE that will enhance clinical care as well as provide insights into the strengths and limitations of therapeutic interventions.

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Eosinophilic Esophagitis: Relationship of Subepithelial Eosinophilic Inflammation With Epithelial Histology, Endoscopy, Blood Eosinophils, and Symptoms

Abstract: There is a significant but modest correlation between subepithelial histologic activity and epithelial histologic activity, endoscopic severity, and symptom severity. The long-term clinical impact of assessing subepithelial alterations in EoE needs to be further elucidated.

Cited by 37 publications

References 31 publications

Eosinophilic esophagitis: latest insights from diagnosis to therapy

Eosinophilic esophagitis: latest insights from diagnosis to therapy

RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis

Clinical relevance of esophageal subepithelial activity in eosinophilic esophagitis

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