Table 2.
Advantages and disadvantages of therapeutic endpoints in eosinophilic esophagitis
| Endpoint | Advantages | Disadvantages |
|---|---|---|
| Symptoms | Addresses FDA guidance regarding patient perspective, intrinsic to disease definition, validation of specific PROs | Dependent upon eating behavior and food modification, sporadic basis of complaints, differences in pediatric and adult symptoms, association with esophageal remodeling rather than inflammation, placebo response |
| Eosinophil density (eos/hpf; eos/mm2) | Objective biomarker, highly reproducible, intrinsic to disease definition, applicable to both children and adults, responsiveness in placebo-controlled trials | Limited correlation with symptoms, heterogeneity in methods to quantify, threshold to define response not established, tissue sampling variability, incomplete measure of disease activity |
| Endoscopic features (EoE Endoscopic reference score, EREFS)(89) | Objective measure, moderate-good inter-observer agreement, responsiveness in placebo-controlled trials, measures “whole organ” activity, correlation with disease activity, applicable to both children and adults | Variability in prevalence of individual features, limited correlation with eosinophil density, threshold to define response not established |
| Quality of life (24, 25,71) | Addresses FDA guidance regarding patient perspective, pediatric and adult instruments validated | Responsiveness to therapy not established, threshold to define response not yet defined, limited correlation with eosinophil density, not able to be used as a clinical trial primary endpoint |
| Comprehensive histologic assessment (composite index of multiple histologic parameters)(80) | Addresses concerns of over - reliance on eosinophil density, applicable to both children and adults | Limited validation, responsiveness to therapy not established, variability in prevalence of individual features, reliance on tissue orientation |
| Esophageal distensibility (radiologic assessment or impedance planimetry)(76,96) | Objective measure of esophageal remodeling, correlation with symptom outcomes | Impedance planimetry not widely available, automated analyses under development, responsiveness to therapy not established |
| Gene expression (95) | Comprehensive assessment of multiple factors involved in pathogenesis | Clinical relevance of molecular readout not established, advantages over eosinophil density not established |