Tag Archives: Eosinophilic esophagitis

Long-Term Effectiveness of Dupilumab for Eosinophilic Esophagitis

Posted on by
Reply

S Oliva et al. Clinical Gastroenterology and Hepatology; 2026 (Epub, 9/7/26). Open Access! Long-Term Effectiveness of Dupilumab in Eosinophilic Esophagitis: Results From the DUPEOETALY Study

Methods: This retrospective observational study included 167 patients, median age, 21.5 years, with EoE from 50 Italian centers, unresponsive or intolerant to conventional therapies. Given the real-world design of the study, no standardized protocol mandated patient re-evaluation at fixed follow-up timepoints. Histologic remission was considered having <15 eos/hpf. All patients, however, underwent at least 3 endoscopic assessments: at baseline, after the induction phase (performed between weeks 12 and 24), and at 1-year follow-up. At baseline, 76% had a personal history of atopy, 86.2% had used corticosteroids, and 94% had used proton pump inhibitors.

Key findings:

  • DSQ score decreased from 22.14 ± 26.63 to 0.21 ± 2.30, EREFS from 4.95 ± 3.43 to 0.07 ± 0.09, and Eos/HPF from 36.80 ± 31.75 to 0.06 ± 0.46.
  • Improvements increased with treatment duration. By week 72, 98.3% of patients achieved remission criteria (DSQ ≤5, Eos/HPF ≤15, and EREFS ≤2). 
  • No serious or systemic adverse events were reported, and no patients discontinued treatment due to intolerance. 
Remission criteria were defined as DSQ ≤5, EREFS ≤2, and <15 eos/HPF,
with complete remission achieved when all 3 were met simultaneously.24

Discussion:

  • “Only a small proportion of patients in our cohort had a history of esophageal dilation (8.4%), which may suggest a relatively lower burden of advanced fibrostenotic disease…could partially influence remission rates and should be considered when interpreting the generalizability of our findings to populations with more severe structural disease.”

My take: This study supports the long-term effectiveness of dupilumab in pediatric and adult patients with EoE. It is not clear why there was such a high remission rate in this cohort compared to previous reports.

Related blog posts:

Some good brief YouTube EoE educational videos for families from GIKids.org (with pharmaceutical funding), links:

How Effective Is Treatment of Eosinophilic Esophagitis In Patients with Rumination Syndrome?

Posted on by

D Yang et al. J Pediatr Gastroenterol Nutr. 2026;83:374–380. Rumination syndrome and eosinophilic esophagitis in children: Defining the relationship

Methods: This was a retrospective cohort study of children with RS and EoE evaluated at our institution from 2016 to 2023.

Key findings:

  • In this cohort with rumination syndrome, 22 of 230 had EoE. This is a significantly greater prevalence of EoE (10%) among children with RS than in the general population (0.1%).
  • Among those diagnosed with EoE first (70%), RS diagnosis occurred after a median of 15.4 months.
  • EoE treatment led to mucosal remission in 73% and improved dysphagia in 41%, but 86% continued to experience regurgitation.
  • RS treatment, including behavioral therapy and baclofen, improved or resolved regurgitation in 64%.
Improvement in Regurgitation to EoE vs RS ‐based treatments among patients with RS and EoE.
EoE, eosinophilic esophagitis;RS, rumination syndrome

Limitations: retrospective design and potential referral/selection bias in a tertiary care population (specialized center for rumination).

My take: In patients with both EoE and RS, regurgitation continued in 86% of patients who achieved EoE remission. Especially in those without dysphagia, most will need treatment of RS in additon to EoE. In addition, earlier treatment of RS may improve outcomes.

Related blog posts:

Optimizing PPI Therapy for Eosinophilic Esophagitis with CYP2C19 Genotyping

Posted on by

P Bose et al. American Journal of Gastroenterology. DOI: 10.14309/ajg.0000000000004117 Dose May Matter: CYP2C19 Genotype and Proton-Pump Inhibitor Response in Pediatric Eosinophilic Esophagitis

Methods: A cohort study of pooled data from 2 tertiary-care pediatric centers (Riley Children’s Health,Indianapolis, IN, and Children’s Hospital of Philadelphia, Philadelphia, PA) was conducted. N=131, mean age 8.5 yrs. Individuals with certain CYP2C19 polymorphisms were classified as normal (NMs), intermediate/slow(IMs), and rapid metabolizers (RMs) of PPIs based on the presence of normal function (*1), loss-of-function (*2), or gain-of-function (*17) alleles. PPI choice and dosing:

Key findings:

  • PPI response occurred in 22.1% of subjects (29/131)
  • Overall, IMs had the highest proportion of PPI response at 33.3% (10/30), followed by NM of 21.7% (13/60) and RM of 14.6% (6/41) (P 5 0.205).
  • No ultra-rapid metabolizers had a response.

Discussion: “Atypical dosing for PPI use in EoE may be related to mechanisms of action apart from gastric acid suppression, such as inhibiting eosinophil migration or restoring esophageal mucosal barrier integrity, which have been previously proposed.”

There may have been a selection bias in this population. The methods section does not detail these cohorts precisely. It is unclear if all patients in these centers undergo CYP2C19 genotype testing. In most centers, CYP2C19 genotype testing is uncommon and may be more likely in those who have not responded to therapy.

My take:

  1. CYP2C19 genotype testing may help determine whether PPI therapy is likely to work for a patient with EoE and influence the dosage selected. This is not a new concept. It was noted at a NASPGHAN meeting in 2017.
  2. In those with unfavorable CYP2C19 genotype, either an alternative therapy or a PPI that is not metabolized with CYP2C19 (eg. rabeprazole) should be considered.

Related blog posts:

Here’s Why CYP2C19 Testing May Be Helpful For Refractory Reflux

Posted on by

Recent pediatric Rome V recommendations suggested the use of CYP2C19 testing in patients with reflux that was not responding to time-limited therapy (link: Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction (Part 1)). The following retrospective study of adults (n=421) at an academic medical center provides a strong rationale.

L Creech et al. Clin Gastroenterol Hepatol 2026; 24: 1550-1557. Open Access! High Prevalence of CYP2C19 Rapid and Ultrarapid Metabolism Among Patients With Gastroesophageal Reflux Disease

Key finding:

  • 44% (n=184) of patients presenting to gastroenterology clinic with gastroesophageal reflux disease who underwent CYP2C19 genotyping were found to be rapid metabolizers (RMs) (38%) or ultrarapid metabolizers (6%)
  • The prevalence of Barrett’s esophagus/erosive esophagitis was higher among ultrarapid metabolizers (24%; n = 5/21) than among normal metabolizers (7%; n = 12/165; odds ratio, 3.5)
  • Among the 184 RMs, 79% (n = 146) had a change in management due to CYP testing results: 65% (n = 120) changed their medication (89 patients were switched to rabeprazole), 22% (n = 41) continued PPI therapy, and 14% (n = 26) increased their PPI dose

Discussion points:

Prevalence of CYP RMs in Other Studies:

  • “Ionovo et al studied over 2 million patients who underwent genetic testing using 23andMe and found that the rate of RMs (∗1/∗17) in the general population was 26.0%, and the rate of URMs (∗17/∗17) was 4.4%.25“
  • “Fricke-Galindo et al analyzed data from 138 studies of over 52,000 healthy volunteers from around the world.26 The highest rates of combined RMs and URMs were reported in the Middle Eastern populations (36%), followed by European (28.6%), African (16.8%), and Asian populations (3.4%).26 The prevalence was 26.7% in the United States.”
  • “Among GI clinical practice guidelines, the 2025 American Society for Gastrointestinal Endoscopy (ASGE) guideline was the first to suggest routine incorporation of CYP testing into the management of patients with GERD.30“
  • “PCABs offer a viable alternative to PPIs in patients who are RMs and should be considered accordingly. PCABs are also not dependent on preprandial dosing and thus are easier for patients to take. However, the cost of PCABs continues to be a limiting factor.”
  • Testing cost: “A typical out-of-pocket price of $250 to $400 and is covered by some insurance.39“
  • Limitations: The study population has a selection bias compared to the general population. Patients referred to a GI clinic are more likely to have treatment-refractory GERD and thus have higher rates of RMs.

My take: In patients with established GERD who are not responding to treatment, CYP testing may be helpful. This is probably true for patients with EoE as well. In patients with GERD who are RMs, options include changing to rabeprazole, higher doses, or possible use of PCABs.

Related blog posts:

Normalizing Diet with Dupilumab Therapy

Posted on by

N Wolfest et al. Clin Gastroenterol Hepatol 2026; 24: 1271-1279. Open Access! Efficacy of Dupilumab on Facilitated Food Reintroduction in Eosinophilic Esophagitis

Methods: This open-label pilot study — patients who demonstrated disease control in the dupilumab run-in stage were able to continue into the food reintroduction stage for a total of 52 weeks. Reintroduction of trigger foods occurred at months 3, 6, and 9, while continuing on dupilumab treatment. Symptoms, histology, endoscopy, and esophageal diameter were compared prior to and following every phase of food reintroduction to month 12. All patients had previously failed trigger food reintroduction on their current EoE medication.

Key findings:

Dupilumab effectiveness: At month 3 of the dupilumab run-in stage, 17 of 19 evaluable patients (89%) per protocol had a PEC (peak eosinophil count) of <6 eos/hpf. One patient had a PEC of 6 eos/hpf but was permitted to proceed to the food reintroduction stage.

Food reintroduction:

  • Reintroduction of an EoE trigger food was successful in 86% of instances (54/63), as defined by a PEC <6 eos/hpf and no symptoms
  • At month 6, 75% of patients (12/16) successfully reintroduced an EoE trigger food, and, as portion size was increased or additional trigger foods were added, 93% (13/14) and 79% (11/14) successfully introduced EoE trigger foods at months 9 and 12, respectively
  • By the end of the study, 5 patients successfully achieved unrestricted serving sizes of an EoE trigger food without worsening esophageal biopsies
  • The mean PEC did not significantly change following food reintroduction at month 6 (5.3 [SD, 8.9]), month 9 (1.3 [SD, 2.8]), or month 12 (2.6 [SD, 4.5]) (see Figures below)

My take (borrowed in part from authors): For most newly-diagnosed patients, the majority prefer medical therapy over dietary restricitons. In those currently managed with dietary restrictions, “dupilumab treatment may provide a safe method for patients with EoE to gradually taper elimination diets for some trigger foods.”

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

How Does Prior Topical Steroids Affect Response to Dupilumab for Eosinophilic Esophagitis

Posted on by

M Chehade et al. Am J Gastroenterol 2026; 121: 649-660. Open Access! Dupilumab Efficacy in Children With Eosinophilic Esophagitis With Prior Swallowed Topical Corticosteroid Use: A Subgroup Analysis Thanks to Ben Gold for this reference.

Background: “The aim of this exploratory, post hoc subgroup analysis of EoE KIDS was to assess dupilumab efficacy and safety in patients aged 1–11 years with EoE previously treated with STCs” [swallowed topical corticosteroids]. This study further examined th EoE KIDS cohort (Chehade M, Dellon ES, Spergel JM, et al. Dupilumab for eosinophilic esophagitis in patients 1 to 11 years of age. N Engl J Med 2024;390(24):2239–51.)

Methods: The trial consisted of the following: part A, a 16-week, randomized, double-blind, placebo-controlled treatment period; part B, a 36-week, extended active treatment period in which patients knew that they received active treatment but did not know their regimen; and part C, a 108-week, open-label extension period in which all patients received higher-exposure dupilumab. Eligible patients were aged 1–11 years with a confirmed diagnosis of active EoE who were unresponsive to ≥8 weeks of PPIs.

Of 102 patients, 82 (80%) received prior STCs and 59 (58%) had prior inadequate response, intolerance, and/or contraindication (IRIC) to STCs.

Key findings:

  • At W16, higher-exposure dupilumab improved rates of histologic remission vs placebo in patients with prior STC use (60.7% vs 0.0%) and prior IRIC to STCs (60.9% vs 0.0%).
  • Responses were maintained at W52 with higher-exposure dupilumab, with improvements observed in patients who switched from placebo to higher-exposure dupilumab.
  • “Findings seemed comparable in those without prior STC use or prior IRIC, although patient numbers were small.” Only 9 patients in the treatment cohort did not haver prior STC use.

My take: It appears that dupilumab works well in those with and without prior swallowed topical corticosteroids (STCs). Though the numbers are small, the response appears more robust in those without prior STCs; perhaps, those with prior STC failure had more refractory EoE.

Some good brief YouTube EoE educational videos for families from GIKids.org (with pharmaceutical funding), links:

Related blog posts:

Beneficial Off-Target Effect: Upadacitinib Improved Eosinophilic Esophagitis (Case Report)

Posted on by

N Nguyen , M Bauer. JPGN Rep. 2026;1-3.  Successful treatment of eosinophilic esophagitis with upadacitinib prescribed for atopic dermatitis. doi:10.1002/jpr3.70170

This case report describes a 15 yo with severe atopic dermatitis and multiple atopic diseases whose eosinophilic esophagitis remained in remission after starting upadacitinib, a JAK1 inhibitor, and stopping dupilumab. JAK1 inhibitors, such as upadacitinib and abrocitinib, are approved for severe AD. 

The discussion notes that there had been a prior case report of tofacitinib, a JAK1/JAK3 inhibitor, effectively treating refractory EoE. The authors “hypothesize that JAK inhibition of key Th1 and Th2 signaling pathways including IL-4, IL-13, and TSLP could effectively treat EoE, while also treating AD.”

My take (borrowed from authors): “If upadacitinib is used for the treatment of AD, cessation of other therapies for EoE, particularly biologics like dupilumab, should be strongly considered.”

Related blog posts:

Eosinophilic Esophagitis: “Fifth Member of the Atopic March”

Posted on by

Since I completed my pediatric residency and pediatric gastroenterology fellowship in Cincinnati, I receive their bulletins. A recent title (Link: EoE: The Fifth Member of the Atopic March) prompted me to review the source article. The Cincinnati summary noted that “children with AD [atopic dermatitis] within the first two years of life are 10 times more likely to develop EoE [eosinophilic esophagitis] by age 8.”

Source article: WC Chang et al. Journal of Allergy and Clinical Immunology 2026; 157: 999-1001. Open Access! Longitudinal enrichment of eosinophilic esophagitis in children with AD: The MPAACH cohort

Background: The atopic march refers to the natural history of allergic disease manifestations as they develop in childhood.1 Classically, the march begins with atopic dermatitis (AD), followed sequentially by food allergy (FA), asthma, and allergic rhinitis (AR),1 but there is significant heterogeneity in the timing, order and organ(s) affected.2 

Methods: Using the Mechanisms of Progression of Atopic Dermatitis to Asthma in CHildren (MPAACH) cohort,4 a US longitudinal early-life cohort of children (n=700) with AD, the authors examined the associated epidemiology of EoE with other members of the atopic march.

Key findings:

  • “Of 700 MPAACH participants, 10 have EoE, and in all cases, EoE developed after AD onset. Of these 10 subjects, 2 had EoE at enrollment, whereas 8 developed EoE subsequent to enrollment in MPAACH”
  • “To date, 48.9% of the children in MPAACH had developed at least 1 allergic comorbidity (FA, AR, and/or asthma) by age 8 years versus 90% of the children with EoE (P = .009), highlighting the strong association between EoE and other atopic diseases”
  • “Despite no difference in skin barrier quality or AD severity, the children with EoE were significantly more likely to have food sensitization (as defined by at least 1 positive result of a skin prick test to a food allergen [60% vs 28% (P = .039)]) and FA (70% vs 13% [P < .001])…suggesting that the esophageal epithelium may be the site of allergen penetration and immune activation, independent of the skin barrier” 

My take: There was a 10-fold higher risk of EoE (1.4% or 10 of 700) in this cohort of children with AD compared to the general population. However, I was expecting a much higher prevalence in this population. This could be due to the fact that patients are seeing me for GI symptoms rather than for AD. It is possible, as well, that the number of EoE patients would be higher if there was a prospective evaluation (e.g. endoscopy).

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

2026 Review: Eosinophilic Gastrointestinal Diseases (EGIDs)

Posted on by

P Visaggi, ES Dellon. Gastroenterology 2026;170:476–494. Open Access! Epidemiology, Natural History, and Treatment of Eosinophilic Gastrointestinal Diseases

Diagnosis:

  • EoE is diagnosed in the setting of symptoms of esophageal dysfunction, demonstration of at
    least 15 eosinophils per high-power field (eos/hpf) on esophageal biopsy, and exclusion of competing causes of esophageal eosinophilia. At the time of diagnosis, disease severity can be assessed with the Index of Severity for EoE (I-SEE)
  • Non-EoE EGIDs: the diagnostic process is more challenging and pediatric diagnostic guidelines were only published in 2024…biopsy specimen shows pathologically elevated
    levels of GI tract eosinophils, and other conditions that cause GI eosinophilia are excluded…Symptoms are nonspecific, multiple conditions could explain extraesophageal eosinophilia, inflammation can involve muscular and serosal layers rather than mucosal,

Treatment:

  • EoE: PPIs, Swallowed topical corticosteroids, Monoclonal antibodies and food elimination dets
  • Non-EoE EGIDs: “The management of non-EoE EGIDs is challenging due to lack of established end points, validated outcomes, and of successful RCTs leading to approved treatments. Accordingly, management of non-EoE EGIDs is currently based on low-quality evidence.” Main treatments: corticosteroids (prednisone or budesonide), food elimination diets, and monoclonal antibodies (eg. dupilumab). “The use of PPIs, mast cell stabilizers, leukotriene inhibitors, and immunomodulators for non-EoE EGIDs has been reported,
    with variable results.”

My take: This is a useful review with a number of pointers for epidemiology, natural history, evaluation and management of EoE and Non-EoE EGIDs.

Related blog posts:

Extent of Eosinophilic Esophagitis and Response to PPI Therapy

Posted on by

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.

Related blog posts: