Editorial: PPI-responsive oesophageal eosinophilia and long-term PPI treatment.

Abstract

Sirs, Similar to erosive gastro-oesophageal reflux disease (GERD) 20 years ago, proton pump inhibitor (PPI) use in oesophageal eosinophilia is shifting from being used for initial healing only to being used as maintenance therapy. Dr Molina-Infante's group present the first data with PPI maintenance therapy in adult patients. For GERD patients with erosive oesophagitis many feel that the dose to heal is the dose required to prevent recurrent disease. This study by Dr Molina-Infante et al. looks at the issue of lowering the dose of PPI treatment in patients with PPI-responsive oesophageal eosinophilia (REE).1 In this study the Spanish group took patients with histologic response to omeprazole at 40 mg twice daily and began a PPI taper, performing endoscopy and oesophageal biopsy 8 weeks after each dose reduction. There were some dropouts along the way, but 81% of those evaluated remained in histological remission on 40 mg once daily dosing and of those eventually tapered down to 20 mg once daily dosing, 83% remained in histological remission. Interestingly, no patient in histological remission developed symptomatic relapse, whereas only half of the patients with oesophageal eosinophilia were in symptomatic remission. This study, therefore, suggests that PPI medications can be tapered in eosinophilic oesophagitis (EoE) and histological remission can be maintained, but this tapering process needs to be done based on histological sampling, rather than according to symptoms. The other important clinical issue with PPI treatment of eosinophilic oesophageal infiltration (EEI) is whether this remission can be sustained over time? Two small reports from the paediatric literature highlighted a loss of response to PPI therapy in some patients over time.2, 3 Until very recently, we had little data to support the long term efficacy of PPI therapy in the maintenance treatment of EoE. In a recent study by this same group of investigators, they looked at tapering the PPI dose down to the lowest that controlled symptoms (60% twice daily, 40% once daily) and found that at that dose 73% of the patients remained in histological remission at a mean follow-up of over 2 years.4 This study, therefore, suggests that PPI remission of EEI can be maintained long-term in the majority of patients. Furthermore, this study also demonstrated that a lack of sustained response to PPI may occur because of hypermetabolism due to a variant CYP2C19 genotype, rather than a primary abnormality of the disease itself. As a result, there may even be a greater population of patients with PPI-REE if the PPI is dosed correctly. The importance of demonstrating that patients with PPI-REE have a sustained response to PPIs cannot be underestimated. Although there is concern about long-term complications of PPIs such as bone, cardiac or renal effects and predisposition to intestinal infections, the general long term safety of these medications when used in GERD is excellent. This may also stand in contrast to the long-term effects of glucocorticosteroids and the difficulty of maintaining an elimination diet, the other two chronic therapies for EoE-related disease. There are also larger looming questions that need to be addressed. Firstly, do PPIs reverse fibrotic disease in patients with PPI-REE, and secondly does 2 years of favourable response predict a lifetime of disease prevention? As EoE appears in most patients to be a chronic unremitting disease, longer term studies of chronic use in PPI-REE will be essential. Nevertheless, this study by Molina-Infante et al. remains an important first step in understanding the role of chronic PPI use in PPI-REE patients and, perhaps, EoE as a whole. Declaration of personal interests: None. Declaration of funding interests: Dr Alexander has research funding from Merck Inc. and a financial interest in Meritage Pharmacia. Dr Katzka has research funding from Meritage Pharmacia, Covidien Inc, and the CURE foundation.