Prolonged Therapy in Eosinophilic Esophagitis Prevents Relapse Without Added Risk
"Proton pump inhibitors appeared more effective than off-label swallowed topical corticosteroids in sustaining histologic and clinical responses."
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09/25/2025
A recent systematic review and meta-analysis found that prolonged therapy in eosinophilic esophagitis (EoE) is safe and helps prevent long-term histologic relapse, with dose reduction from induction to maintenance not associated with significant drawbacks.
“Evidence from randomized trials indicates that biologic therapies and swallowed topical corticosteroids are similarly effective in maintaining histologic and symptomatic control in patients with eosinophilic esophagitis over a follow-up period of up to 1 year,” reported Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and Amsterdam University Medical Center, the Netherlands, and colleagues. “In observational studies, proton pump inhibitors appeared more effective than off-label swallowed topical corticosteroids in sustaining histologic and clinical responses, although heterogeneity in follow-up timing, study designs, disease stages, and dosing regimens may have influenced the results for off-label swallowed topical corticosteroids.”
They added, “Safety analyses reported a low rate of adverse events in the long term; therefore, the fear for side effects should not prompt discontinuation.”
Study Details
According to Dr. Barchi and fellow investigators, recent data have demonstrated the short-term effectiveness of corticosteroids, particularly newer formulations with esophageal delivery, as well as biologics, in inducing histologic response in patients with EoE. However, they acknowledged that evidence in maintenance therapy indications remains limited.
The investigators thus conducted the present analysis, beginning with a systematic literature search to identify eligible studies in the PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials electronic databases. Studies were included if they involved patients with EoE, symptoms of esophageal dysfunction, and an eosinophil count of at least 15 per high-power field on index esophagogastroduodenoscopy biopsies who underwent initial induction therapy with a recommended drug regimen and continued it for a median follow-up of at least 48 weeks.
A total of 23 studies were considered in the final analysis (randomized controlled trials: n = 9; observational prospective studies: n = 6; retrospective analyses: n = 8). Long-term outcomes were reported for 1,819 patients, including 422 pediatric patients from 7 studies and 1,397 adult patients (aged > 12 years) from the remainder.
The primary outcome was the pooled rate of histologic success (defined as < 15/< 6 eosinophils/high-power field) at the end of available follow-up. Risk ratios for achieving histologic success with maintenance therapy compared with placebo or induction therapy, along with drug safety, were also evaluated. Random-effects meta-analyses were conducted. Results from randomized controlled trials and observational studies were analyzed separately.
Clinical and Histologic Outcomes
In randomized controlled trials, 86% of patients treated with corticosteroids achieved eosinophil counts under 15 per high-power field, and 79% of those who received biologics reached this threshold. The rate with dupilumab alone was 82%, whereas small molecule inhibitors yielded 28%. Treatment with biologics (70%) versus corticosteroids (59%) showed a higher rate of eosinophil counts under 6 per high-power field. The clinical success rates with corticosteroids and biologics were 58% and 59%, respectively.
Budesonide was found to be associated with a common-effect adjusted risk ratio of 7.87 for maintaining histologic remission over therapy discontinuation.
In observational studies, proton pump inhibitors demonstrated 64% histologic and 80% clinical success. These rates were 49% and 51% with corticosteroids, respectively. Therapy deescalation was not found to be associated with histologic relapse.
Safety Outcomes
According to the investigators, long-term safety was confirmed, with a rate of severe adverse events of 3% in randomized controlled trials and 5% in observational studies. They noted treatment withdrawal rates of 10% and 4% in the abovementioned study types, respectively.
Moderate to substantial heterogeneity was reported for most outcomes.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators noted. “Corticosteroids and biologics are equally effective (86% and 79%) in maintaining histologic remission (≥ 48 weeks) in randomized trial settings, with a relative risk of 7.8 of prolonging remission versus discontinuation. Observational data are scarce, with proton pump inhibitors showing discrete histologic and clinical efficacy (64% and 80%).”
They continued, "studies investigating outcomes of prolonged maintenance treatment are needed to identify proper drug regimens and dosages that may limit adverse events and improve compliance. Research questions that remain to be addressed by future studies include if a subset of patients with eosinophilic esophagitis that can discontinue treatment can be identified, if there is an optimal drug for maintaining long-term remission optimizing side effects, and at what dosage."
Dr. Barchi reported no conflicts of interest. For full disclosures of the other study authors, visit the link below.
Summary content
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The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.