Category Archives: eosinophilic esophagitis

Misleading Study on Topical Steroids for Eosinophilic Esophagitis -Comparing Four Apples to One Apple

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FB Murray et al. Am J Gastroenterol 2026; 121: 130-139. Loss of Response to Off-Label Swallowed Topical Corticosteroids in Eosinophilic Esophagitis Can be Overcome by a Switch to an Esophageal-Targeted Budesonide Formulation

A quick glance at this study gives the impression that off-label swallowed topical corticosteroids (olSTC) are an inferior treatment to the budesonide orodispersible tablet (BOT) as many patients who had either a non-response to olSTC achieved remission with BOT.

Methods: This study from the Swiss Eosinophilic Esophagitis Cohort Study with 340 patients (mean age 43 years) analyzed prospectively collected data. Twenty-six percent had prior olSTC nonresponse (n=66) , 16% were in remission with prior olSTC (n=44), and 58% were STC-naïve.

Here were the key results according to the authors (Figure 2):

  • Histologic remission (<15 eos/hpf) was achieved in 62% who had not responded to olSTC previously and in 72% who had prior olSTC response (P=0.094)
  • The authors conclude that “our results provide conclusive evidence that off-label STC cannot be translated into corticosteroid-refractory disease per se.”

Here’s the main problem with this study:

  • “Most patients in Switzerland have been treated with a rather low-dose olSTC regimen (</ = to 0.5 mg per day).” Typical BOT dosing is 2 mg per day. Thus, the authors are comparing the use of 4-times the amount of budesonide in the BOT group to the olSTC non-responders.
  • Their discussion states that “most patients with EoE without a response to olSTC are not truly corticosteroid-refractory but respond to an esophageal adjusted topical corticosteroid formulation…In the United States, a BOS [suspension] has been recently approved…Due to similar mechanism of action, it can by hypothesized that patients without prior response to olSTC will respond to BOS in similar rates as shown in our study.” Yet, there is no proof that the formulation made a difference in this study; the more likely explanation is that patients previously who had not responded to olSTC were under-treated.

My take:

  1. In patients with eosinophilic esophagitis who have not responded to topical steroids, it is important to make sure that they were prescribed the right dose and that they are actually taking the medication.
  2. Future studies of esophageal formulations should be compared to off-label STC using the same dose to determine if the formulations confer additional benefits.
  3. Getting the right dose is important for every malady.

Thanks to Ben Gold for sharing this publication with me.

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Cerro Torre Hike, El Chalten

Extent of Eosinophilic Esophagitis and Response to PPI Therapy

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DA Hartnett et al. Clin Gastroenterol Hepatol 2026; 24: 375-384. Open Access! Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis

Methods: This was a retrospective cohort study of newly diagnosed adult patients with EoE — All patients received ≥8-week PPI trial and underwent repeat biopsies to assess response. There were including 66 with isolated distal and 200 with proximal/diffuse disease. 86% of patients received twice daily PPI therapy (73% in those with isolated distal disease and 87% in the diffuse/isolated proximal disease.

Key findings:

PPI response was higher among patients with isolated distal disease:

  • histologic remission [<15 eosinophils/hpf post-PPI]: 63.6% vs 44.5%; P = .01
  • deep remission [<6 eosinophils/hpf]: 54.5% vs 31.0%; P = .001
  • symptom improvement: 92.4% vs 81.0%; P = .03).

The discussion noted that there has been limited studies of EoE distribution and response to treatment. “Godat et al observed that the distribution of esophageal eosinophilia had no impact on clinicohistologic remission rates (defined as ≤2 on a scale of 0–10 for dysphagia/odynophagia in the last 7 days and a peak eosinophil count <5 eos/hpf) in patients treated with budesonide orodispersible tablets.19“

“The generally higher PPI response with isolated/predominant distal disease suggests that acid suppression and improved mucosal barrier function likely play a key role in how PPI may lead to EoE remission…prior studies have demonstrated no correlation between findings on ambulatory pH monitoring and PPI response in EoE.25 Therefore, the differential response to PPI based on eosinophil distribution phenotypes may be due to more than comorbid GERD alone.”

My take: While the pathophysiology of how PPIs work for EoE is unclear, it appears that the response to PPIs is better with in those with isolated distal EoE. The difference in response may have been even more pronounced if both groups had a similar percentage of receiving twice daily PPI treatment.

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Is Topical Budesonide Less Effective in Patients With Eosinophilic Esophagitis With Strictures?

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I Hirano et al. American Journal of Gastroenterology 2025; 120(7):p 1502-1510. Open Access! Effect of Esophageal Dilation History on Efficacy Outcomes in Patients With Eosinophilic Esophagitis Receiving Budesonide Oral Suspension

Methods: This post hoc analysis assessed data from a 12-week, randomized, double-blind, placebo-controlled phase 3 study (NCT02605837) of budesonide oral suspension (BOS) 2.0 mg twice daily in patients (n=318) aged 11–55 years with EoE and dysphagia. Coprimary efficacy outcomes were histologic (≤ 6 eosinophils per high-power field [eos/hpf]) and dysphagia symptom (≥ 30% reduction in Dysphagia Symptom Questionnaire scores from baseline) responses at week 12.

Key findings:

  • Histologic responses (≤ 6 and < 15 eos/hpf) were similar regardless of dilation history
  • Fewer BOS-treated patients with dilation history than no dilation history achieved a dysphagia symptom response (44.0% vs 59.0%)

Discussion Points:

  • “Esophageal dilation may provide immediate relief from dysphagia (15); symptom improvement has been observed in 95% of dilated patients with EoE (29)…[however] dilation does not affect the underlying inflammation (18).”
  • “A histologic response (<15 eos/hpf) to swallowed corticosteroids has also been associated with a reduced number of repeat esophageal dilations required to maintain a similar esophageal caliber compared with nonresponse (≥15 eos/hpf)…this supports swallowed corticosteroid use in patients who have undergone esophageal dilation, even in the absence of acute symptom improvement.”
  • “Study limitations include potential enrollment of patients with severe disease due to stringent inclusion criteria.”

My take: While dilatation alone often improves symptoms, treatment with budesonide may help reduce need for repeat dilatations.

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Etrasimod for Eosinophilic Esophagitis?

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ES Dellon et al. Lancet Gastroenterol Hepatol 2025; 10: 622–33. Etrasimod as a treatment for eosinophilic oesophagitis (VOYAGE): a double-blind, placebo-controlled, randomised, phase 2 trial

Background: “Etrasimod is an oral, once-daily, selective S1P1,4,5 receptor
modulator for the treatment of moderately to severely active ulcerative colitis and in development for the treatment of other immune-mediated inflammatory diseases. Etrasimod prevents trafficking of lymphocytes to inflamed mucosal tissue and sites of primary disease
manifestation, offering a unique, promising mechanism for the treatment of eosinophilic oesophagitis.”

There were 108 participants in this study: 41 patients received etrasimod 2 mg, 39 received etrasimod 1 mg, and 28 received placebo.

Key findings:

  • Median percentage changes from baseline in peak eosinophil count (PEC) at week 16:6 were −58·4% for etrasimod 2 mg (p=0·010 vs placebo), −39·4% for etrasimod 1 mg (p=0·29 vs placebo) and −21·5% for placebo.
  • Significant reductions from baseline in oesophageal PEC were achieved with both etrasimod
    doses (n=27 for 2 mg n=28 for 1 mg) at week 24 versus placebo (n=19), with a numerically larger reduction seen with the 2 mg dose, which had a median placebo-adjusted difference of –103·9% from baseline in oesophageal PEC. Oesophageal PEC did not decrease further with longer etrasimod treatment during the extension period (to 52 weeks in a smaller subset)
  • Etrasimod 2 mg was associated with a significant improvement in DSQ score at week 24 versus placebo in patients with no history of dilation (LS mean −21·6 vs –9·6, p=0·031)
  • No serious treatment-emergent adverse events occurred.

My take (borrowed from the authors): “This [phase 2] study provides the first evidence
that targeting the S1P pathway can improve disease activity in eosinophilic oesophagitis. Given that current treatment options for eosinophilic oesophagitis have variable and incomplete response rates, etrasimod presents a promising option.” Larger studies are warranted.

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Budesonide Tablet vs Off-Label Corticosteroids in Eosinophilic Esophagitis

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G Pellegatta et al. Clin Gastroenterol Hepatol 2025; 23: 1058-1060. Open Access! Switch From Off-Label Swallowed Topical Corticosteroids to Budesonide Orodispersible Tablets in Eosinophilic Esophagitis Patients

Methods: This was a single center, prospective, observational study with adult patients previously diagnosed with EoE. Thirty EoE patients, receiving off-label swallowed topical corticosteroids (STCs), were consecutively enrolled. “This is the first study to evaluate the clinical, histological, and endoscopic efficacy of the switch from STCs to BOT [Budesonide Orodispersible Tablet]”

Key findings:

  • The median Dysphagia Symptoms Score decreased from 5 (range 0–9) under STCs therapy to 0 (range 0–6) under BOT therapy (P < .0001)
  • After switching to BOT, there was a significant increase in the number of patients in histological remission (STCs: n = 19 of 30 [63.3%] vs BOT: n = 27 of 30 [90%]; P = .030) and histological deep remission (STCs: n = 17 of 30 [56.6%] vs BOT: n = 25 of 30 [83.3%]; P = .047) 
  • Another important improvement following the switch was the improved patient satisfaction with the therapy in terms of a faster and easier modality of assumption…favors a better compliance to BOT
  • There was a “slight increase in oral Candida infection after BOT”

The authors did not include any cost information regarding the switch. In U.S., BOT is not an available treatment option. However, Eohilia, which is a budesonide suspension with a 12-week FDA approval period, costs ~$2100 per month (for 600 mL =30 day supply), whereas budesonide ampules at same dosage cost ~$300 per month (60 1 mg ampules).

My take: BOT therapy, which was targeted for esophageal delivery, was associated with better response rates. However, the cost of targeted FDA approved budesonide therapy in U.S, is exorbitant.

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Impact of Disease Severity on Eosinophilic Esophagitis Treatment Responses

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CC Reed et al. Clinical Gastroenterology and Hepatology 2025; Worsening Disease Severity as Measured by I-SEE Associates With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis Patients

This was a retrospective study with children and adults with eosinophilic esophagitis (EoE). Among 1312 patients, there were 657 (50%), 461 (35%), and 194 (15%) with mild, moderate, and severe disease by I-SEE, respectively. Disease activity was categorized as mild (I-SEE 1–6), moderate (I-SEE 7–14), or severe (I-SEE ≥15).

Key findings:

  • Patients with severe disease were less likely to have histologic response (49% (severe) vs 55% (moderate) vs 64% (mild); P = .03 for <15 eosinophils per high-power field) 
  • Patients with severe EoE also had lower global symptom response rates (53% vs 79% vs 83%, respectively) and higher post-treatment EoE Endoscopic Reference Scores (EREFS; 3.6 ± 2.3 vs 2.4 ± 1.8 vs 1.6 ± 1.6, respectively)

My take: More severe disease is harder to treat with EoE (and most everything else too).

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Link: I-SEE Tool Scoring Table

Crazy wiring in Chiang Mai, Thailand (but prevalent in many areas of Thailand)

Delivery Vehicle and Outcomes for Budesonide-Treated Eosinophilic Esophagitis

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N Lendner, et al. J Pediatr Gastroenterol Nutr. 2024;79:92‐99. Comparison of budesonide vehicles in inducing histologic remission in pediatric eosinophilic esophagitis.

This retrospective study with 111 patients with EoE examined histologic remission with oral viscous budesonide (OVB) and various delivery vehicles (Splenda, honey, syrup or applesauce). Key findings:

  • Overall rate of histologic remission with OVB was 52.6% (“which is less than the reported response of approximately 66% for topical steroid therapy”).
  • There was no difference in rates of histologic remission or response in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission or response

My take: It does not seem to matter which delivery vehicle is used for OVB; thus, clinicians should aim for more palatable and cost‐effective vehicles.

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When To Take Fewer Biopsies With Eosinophilic Esophagitis

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A Godat et al. Clin Gastroenterol Hepatol 2024: 22: 1528-1530. Eosinophil Distribution in Eosinophilic Esophagitis and its Impact on Disease Activity and Response to Treatment

In this post hoc analysis of the EOS-1 and EOS-2 trials with 263 adult patients, the authors analyzed eosinophil distribution and impact on treatment. Key findings;

  • Peak eosinophil count was highest in the distal esophagus (median 166 eos/mm2) followed by mid esophagus (142) and then proximal esophagus (113). 46% of patients had highest peak eosinophil count in the distal esophagus, 33% in the mid esophagus, and 21% of patients in the proximal esophagus
  • Diagnosis: a biopsy protocol using only distal esophagus would have missed EoE diagnosis in only 13 (4.9%) of patients
  • Remission rates stratified by histologic categories were not statistically different base on disease location: 73% distal esophagus, 76% mid esophagus, 64% proximal esophagus, and 64% diffuse esophageal disease
  • None of the following factors affected treatment outcome: histologic location category, histologic disease severity (peak eos count) and atopic status. For example, treatment failure occurred in 37% without atopy and 30% with atopy

My take: In this study population, separate evaluation of biopsies by location modestly increased the diagnostic yield at baseline. Thus, additional biopsies at disease onset is a good idea. However, the actual distribution of disease activity did not seem to help provide any insight into therapeutic response (to budesonide). Practical implications are that fewer biopsies on follow-up endoscopy may be reasonable to help determine a treatment response.

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Food-Specific IgG4: With This Guided Testing, You Can Achieve the Same Results As Those Who Don’t Have This Testing

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On first glance at this article, it looks like the authors have found that testing for food-specific IgG4 (FS-IgG4) could be useful in guiding dietary treatment for eosinophilic esophagitis (EoE). However, the data don’t support this conclusion.

Methods: Prospective observational cohort in adult patients with EoE (n=22 along with 13 controls) placed on elimination diet based on FS-IgG4 levels (ImmunoCAP, cutoff of 10 mgA/L).

Key findings:

  • Elevated serum FS-IgG4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination
  • Nine (45%) patients had histological remission (<15 eosinophils per high-power field)
  • Serum FS-IgG4 did not decline by 6-week follow-up. In addition, there was no difference in the FS-IgG4 levels between active and inactive EoE
  • 19 of 22 (86.4%) patients had high FS-IgG4 to milk and 13 of 22 (59.1%) had high FS-IgG4 to wheat. No patients required seafood elimination

The authors note in their introduction that total IgG4 levels in the esophagus are 45-fold those of healthy controls. In addition, “a preliminary study assessing trigger foods in patients undergoing 6FEDs has demonstrated elevated FS-IgG4 was associated with trigger foods in esophageal secretions but not foods that did not trigger esophageal eosinophilia” (K Peterson et al. Aliment Pharmacol Ther 2020; 52: 997-1007).

Despite the lack of any proven efficacy of this FS-IgG4-directed diet (over empiric elimination), the editorial suggests that FS-IgG4 levels may be beneficial, noting that the histologic remission rate increased to 64.3% after excluding ~30% patients with concerns of non-adherence. Removing 30% of patients to get better results would often be called “cherry-picking.”

In addition, neither the editorial (nor the study) delves into the fairly high rates of FS-IgG4 to milk and wheat. This suggests that FS-IgG4 testing will be unreliable with numerous false-positives (though there is wide range of reported reactions to milk and wheat in the literature). Even the control group had high FS-IgG4 to milk in half of the patients. Both the editorial and the study review the limitations which include small sample size, need for control group with atopy, and a lack of established cutoff values for FS-IgG4.

My take: This is a NEGATIVE study. Using FS-IgG4 levels to guide elimination diet was NOT better than empiric elimination of either 1 or 2-food groups. This finding should be more clearly stated in both the study and the editorial. It would be very useful to provide specific dietary advice to our patients with EoE. It is possible that a larger study with higher cutoff levels could find some utility for FS-IgG4. However, this study does not make this approach look terribly promising.

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Dupilumab (Dupixent) for Young Children with Eosinophilic Esophagitis (Published Data)

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M Chehade et al. NEJM 2024;390:2239-2251 Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age

This study provides published data that has been referenced previously at time of FDA approval and prior meetings (see posts: Dupixent Approved in Younger Children (15 kg+), Dupixent for Eosinophilic Esophagitis (1-11 yrs) and Clinical Diagnosis of Rumination from DDW Tweets).

Methods:

  • Part A -In this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age (n=102) with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups)
  • Part B- At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks  

Key findings:

  • In Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group
  • The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo
  • The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A
  • Similar adverse effects were noted across all groups. There was an increased rate (at least 10%) of COVID infections in participants receiving dupilumab whereas the incidence of vomiting was at least 10 percentage points lower among patients who received dupilumab (either group) than among those who received placebo 

My take: Dupilumab is an effective option for eosinophilic esophagitis.

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