Long-term treatment in eosinophilic esophagitis: continue, taper, or stop?

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder characterized by symptoms of esophageal dysfunction together with histological evidence of eosinophilic infiltration of the esophageal tissue.1 Since its initial description, awareness has increased among physicians and patients, accompanied by rising incidence and prevalence across all age groups and some geographical regions (mainly North America, Europe, and Australia).2 Uncontrolled inflammation may lead to fibrostenosis and esophageal remodeling,3,4 increasing the risk of food impactions and stricture formation, often requiring repeated dilations.5 Accordingly, the primary therapeutic objective is two-fold: to induce clinical and histological remission and to prevent disease progression and complications by maintaining remission. A recent network meta-analysis demonstrated that the novel orally dispersible formulation of budesonide (BOT) achieved the highest efficacy in inducing clinical and histologic remission, with a relative risk of 0.08 for histologic relapse and 0.5 for clinical relapse, at a dose of 2 mg/day.6 While the swallowed topical corticosteroids (STCs) are efficient and generally safe, high-dose proton pump inhibitors (PPIs) also achieved meaningful remission rates (>50% of histologic remission and >65% of clinical improvement).7 It is therefore reasonable to consider a high-dose PPI trial, particularly in patients with reflux symptoms, evidence of gastroesophageal reflux disease (GERD) signs and predominantly distal esophageal eosinophilia.8 On the other hand, the dual aim of EoE treatment frames the ongoing debate on whether, how, and for how long maintenance therapy should be continued, as highlighted by recent guidelines.9 The recently updated American College of Gastroenterology (ACG) guidelines10 strongly recommend the continuation of maintenance therapy after achieving initial remission, ideally using the same therapeutic class at the lowest effective dose. This stance is grounded in the realization that EoE relapses are very common upon cessation of treatment.11,12 In clinical practice, both patients and physicians often underestimate the importance of maintenance therapy, patients by tapering or discontinuing treatment once symptoms improve, and physicians by not always emphasizing or fully recognizing its long-term value.13 This raises the need for a clearer communication strategy and improved patient and clinicians’ education and cooperation. Key questions remain: are dose reductions feasible for patients in remission and can any subgroup safely discontinue treatment without long-term harm?10 Until recently, robust data on EoE relapse after treatment discontinuation were limited. In a phase 3, double-blind, placebo-controlled trial, maintenance therapy with orally dispersible BOT was compared with treatment withdrawal (placebo). Only 4% of patients in the placebo group maintained histological remission after 1 year, compared to 75% in the BOT group.14 Another withdrawal trial, involving a different BOT formulation (oral suspension) produced similar results, with >50% of patients who experienced disease relapse after treatment discontinuation compared to only 16.7% among those who continued the treatment.15 In a recent systematic review and meta-analysis incorporating all the relevant long-term management studies (with different drug regimens), we found that discontinuing treatment carried a 7.8-fold increased risk of histological and symptomatic relapse compared to maintenance therapy.16 This robust estimate supports earlier observational findings and reinforces the notion that EoE is unlikely to remain in sustained remission without ongoing therapy. Importantly, the meta-analysis also compared trial settings to real-world practice, highlighting that treatment de-escalation, usually halving the induction dose, remains a pragmatic approach to minimize drug burden while keeping patients disease-free.16 Several studies showed only slight reductions in remission rates after dose reduction, both with PPIs17 and older STCs.18 We have shown a non-significant risk of relapse after de-escalation with both PPIs (RR 1.28) and STCs (RR 0.94).16 It’s nonetheless relevant to point out that even in the cases of correctly prolonging the maintenance treatment with adequate follow-up, relapses are not uncommon, particularly with PPIs. Alexander and colleagues recently published a retrospective evaluation of >100 patients on PPI maintenance treatment, showing that, even if the highest relapse rate was found among those with treatment withdrawal (82%), also those patients continuing PPI treatment with high dose a 33% of histological relapse was reported.11 Furthermore, a worrisome 34% rate of histological recurrence in asymptomatic patients added strong evidence in favor of regular endoscopic follow-up.11