Editorial: management of eosinophilic oesophagitis – efficacy vs. effectiveness. Authors’ reply

Abstract

We thank Frazier et al. for their insightful commentary concerning our paper concerning the treatment outcome of adult patients with eosinophilic oesophagitis (EoE).1, 2 We agree with much of the analysis, although a few clarifications appear justified. The use of twice daily proton pump inhibitors (PPIs) for 8 weeks prior to the diagnosis of PPI-responsive oesophageal eosinophilia is (as eloquently summarised by Frazier et al.) an arbitrary intervention based upon the GERD treatment paradigm. Indeed, so called ‘step – down’ therapy, where the dose of PPI is reduced (and remission sustained in most patients) suggests that lower doses may be effective in treating the oesophageal eosinophilia.2 The mechanism whereby PPI's exert their therapeutic effect is of ongoing debate, and effects distinct from the ability to decrease gastric pH appear possible, including the ability to downregulate eotaxin-3 expression.3 It may however be premature to conclude that the ability of PPIs to increase gastric pH plays no part in treatment response. It is not unreasonable to propose that decreasing refluxate of acidic, and thus erosive, gastric contents will improve barrier integrity and lessen food antigen interaction with the immune system.4 Evolving research appears aimed at determining the significance of proposed impairments in barrier function in this patient group.4 Frazier et al. point out a number of potential limitations in study design including that perceived as a lack of treatment standardisation, no symptom report measures, and an intensive endoscopy protocol. It is our belief that treatment was standardised both in terms of dose and duration of medication (esomeprazole 40 mg PO BD or budesonide 1 mg PO b.d.), duration and sequence of dietary reintroduction, that endoscopic surveillance was the minimum necessary, and not dissimilar to previous studies, and that symptom report correlates poorly with disease relapse in any case.5 Furthermore, we utilised minimally invasive transnasal endoscopy without sedation in some patients.6 In the future, alternatives such as cytosponge may decrease the need for endoscopy.7 The difference between effectiveness and efficacy appears to hold particular significance when considering the steps required to institute successful dietary therapy in EoE. Previous studies had conclusively demonstrated that resolution of oesophageal eosinophilia can be achieved with dietary ‘restriction’.8, 9 What had been overlooked was the need to ‘reintroduce’ foods (requiring multiple gastroscopies) and then ‘maintain’ a diet. A clearer perspective of the difficulties likely to be encountered is thus achievable if this process is considered to entail multiple steps. The results of our study are testament to the real world difficulties of such a regimen. The authors’ declarations of personal and financial interests are unchanged from those in the original article.2