New aspects of PPI therapy for EoE are revealed in the EoE CONNECT collaborative registry

PPIs currently constitutes the most commonly used first-line therapy in EoE, mainly due to its safety profile and low cost. An article based on data from patients registered in EoE CONNECT, the largest multicentre registry of patients with eosinophilic oesophagitis (EoE), has been recently published in Alimentary Pharmacology & Therapeutics, one of the most important journals in the Gastroenterology field. The study assessed the efficacy of proton pump inhibitors (PPI) as a therapy for EoE by analysing the data obtained from 630 patients of all ages included in the EoE CONNECT registry who were recruited at 13 hospitals in Spain, Italy and Denmark. Although the ability of PPI to reduce both symptoms and eosinophilic infiltration in the oesophageal mucosa had been repeatedly documented, many aspects related to the efficacy of PPI were still unknown. Different from previous observational studies that assessed PPIs in small series of patients, EoE CONNECT data allowed to evaluate the effectiveness of PPIs in a huge among of EoE patients treated in real-world clinical practice, either as first-line option or after failure to other therapies (including dietary interventions or swallowed topic steroids). This was the key point that enabled the authors to clarify some of the many questions that remained regarding this PPIs as an effective anti-inflammatory approach for EoE.

According to this study, PPI therapy reduced eosinophil density below the diagnostic threshold of 15 eosinophils per high-power field (eos/hpf) in 48.8% of patients, with 37.9% of patients achieving deep histological remission (<5 eos/hpf). A further decrease in eosinophil count from baseline was documented in 4.1% of patients despite no histological remission. Regarding clinical response, PPI therapy induced symptomatic improvement in 71.0% of patients. When both responses were considered together, clinico-histological remission was achieved in 48.9% of the patients.

As new knowledge from this research, double doses of PPI were more effective than standard doses (49.2% vs. 35.8%, respectively). Also, treatment duration between 10 and 12 weeks was more effective than shorter duration of 8-9 weeks) (65.2% vs. 50.4%, respectively). No significant differences were found among the different PPI drugs in achieving clinico-histologic remission when used at high doses. Patients with stricturing phenotype or those who showed fibrotic features at baseline endoscopy (rings and/or strictures) had lower chances of achieving clinico-histological remission with PPI therapy. When analysed together, duration of treatment and EoE phenotype were the most determinant variables to achieve a successful outcome of PPI therapy for induction of remission in EoE.

The study also assessed data from 138 patients who underwent reduction of PPI doses after achieving clinico-histological remission of EoE. Low doses of PPI were effective in maintaining EoE in remission in 70% of patients. Again, a trend towards lower response rates were observed in patients with a stricturing phenotype and those who achieved partial histological remission (5 to 14 eos/hpf in oesophageal biopsies) instead of deep remission (less than 5 eos/hpf) after initial therapy with PPIs.

To summarize, this collaborative study provides evidence that PPI are an effective anti-inflammatory therapy to achieve histologic and clinical remission in half of patients with EoE; among initial responders to double PPI doses, 70% will maintain long term remission after dose reduction. The highest benefit for induction of remission was accomplished with high doses of PPI used for between 10 and 12 weeks in patients without fibrotic findings at endoscopy. Patients with stricturing EoE were less likely to respond to PPI therapy initially and in the long term, so they should be considered candidates for alternative anti-inflammatory options. Collaborative studies such as EoE CONNECT are essential to assess the efficacy of therapeutic interventions in clinical practice, to elucidate many important questions that clinicians and patients must answer when faced with EoE.