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

Reduced Dosing of GLP-1 RAs May Work for Maintenance Treatment of Obesity

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Roni Rabin, NY Times 3/5/26: Most Patients Keep Weight Off With Fewer GLP-1 Shots, Study Finds

An excerpt:

After 36 weeks of follow-up, most of the patients who spaced out their GLP-1 injections kept the weight off and also maintained health benefits like reduced blood pressure and better blood sugar control…

The study was small, only 34 patients in a relatively homogeneous group — mostly white and privately uninsured… the research, published in February in the journal Obesity, provides a potentially appealing new option for patients who are loath to commit to lifelong weekly injections of a costly medication that may not be covered by insurance and that some fear could have unknown side effects…

The patients reduced the frequency only after achieving their desired weight loss and reaching a weight-loss plateau.

My take: In some patients, less frequent dosing of GLP-1s may be effective as maintenance therapy. Whether this strategy could be applied to the daily oral semaglutide is not clear.

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Victoria Island, Bariloche Argentina

How to Score the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Properly

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J Blackwell et al. Gastroenterol 2026; 170: 452-455: Open Access! A Normal UCEIS Is Zero: A Score Divided by a Common Language

“The index uses a Likert scale of vascular pattern, bleeding, erosions and ulcers, with a total score intended to reflect severity of disease. When the index was first published, the baseline score for each descriptor was 1, meaning that a normal vascular pattern, no bleeding, and no erosions or ulcers scored 3. However, when the index was subsequently validated, the values attributed to each descriptor were rebased to 0, to improve clinical utility…This means that a completely normal flexible sigmoidosopy scored 0 rather than 3, and the worst activity of UC ever seen by the investigators (compared with a visual analogue scale 0 to 100) was 8 rather than 11…

The UCEIS has since been shown to predict the need for escalation of medical treatment and has recently been incorporated into a validated prognostic clinical index to predict response to intravenous steroids among patients with acute severe UC.10,11 Accurate scoring is therefore essential, with direct implications for clinical decision making.”

My take: The UCEIS is more detailed than the Mayo score. However, I expect that before long artificial intelligence will be able to review images and give a more consistent interpretation of the severity of endoscopic findings than either of these scoring systems.

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GLP-1 Use Associated with Lower Risk of Colon Cancer

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C Jones. J Clin Oncol 44, 2026: suppl 2; abstract 18 (presented at ASCO 2026). Open Access! GLP-1 receptor agonist vs aspirin for primary prevention of colorectal cancer: Evidence from a real-world head-to-head comparison

Methods: Using de-identified data from TriNetX, which encompasses 150 million patients across 106 health organizations. GLP-1RA users were matched to aspirin users utilizing propensity score matching. The index date was defined as the first documented prescription or administration of either therapy, with follow-up beginning 6 months post-index event. Median follow-up was 2,153 days for GLP-1RA users and 1,743 days for aspirin users. 281,656 patients were analyzed (140,828 per cohort).

Key findings:

  • Colorectal cancer (CRC) incidence was 0.13% (183/140,758) in GLP-1RA users vs 0.176% (247/140,692) in aspirin users
  • GLP-1RA use was associated with a 26% lower risk of CRC [RR: 0.741 (0.612–0.896)].This benefit was consistent across sensitivity analyses at 12 months [RR: 0.738 (0.605–0.900)] and 36 months [RR: 0.779 (0.620–0.979)]
  • Four different GLP-1s were analyzed: HR of 0.436 for liraglutide, 0.471 with dulaglutide, 0.631 with semaglutide, and 0.711 with tirzepatide

The exact mechanism where GLP-1s may exert a protective effect is unclear; perhaps, it is related to a reduction in adverse metabolic parameters and inflammation.

My take: Potential chemopreventive effects are unlikely to be a reason to use GLP-1s in the near future, but may be an added benefit.

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Bariloche, Argentina

Should You Do a Gut Microbiome Test? No — Here’s Why

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J McCreary. MedPage Today; 2/26/26. Open Access! Same Stool Sample, Different Results in Gut Microbiome Tests

An excerpt:

“Direct-to-consumer gut microbiome tests produced markedly different results — even when analyzing the same stool sample, researchers found.

Identical fecal samples sent via 21 home-testing kits to seven anonymized direct-to-consumer testing companies yielded a wide variation in reported bacterial abundance and in the health assessments generated from those data, reported Stephanie L. Servetas, PhD, of the National Institute of Standards and Technology (NIST) in Gaithersburg, Maryland, and colleagues in Communications Biology.

In some cases, there was not even agreement among kits produced by the same company…

When researchers compared 18 commonly reported microbial genera across companies, no single provider aligned with the consensus profile for all 18. Across the full dataset, 1,208 unique taxa were reported, but only three genera appeared in every company’s results…

The authors said the discrepancies likely stem from differences in sample processing, sequencing methods, bioinformatics pipelines, reference databases, reporting thresholds, and quality control standards…

“These tests have become popular, partly because people, I think, are increasingly interested in health and wellness, and partly because the gut microbiome has been linked — at least in the public imagination — to the idea that you can improve a whole range of conditions through diet and lifestyle changes,” said co-author Diane Hoffmann, MS, JD, of the University of Maryland in Baltimore.

“There’s been a lot of hype around that, but the hype doesn’t really match the evidence. These tests often have limited evidence behind them, especially when it comes to informing clinical decisions or even basic dietary recommendations,” she added. “So the marketing can be questionable, and consumers can end up misinterpreting or over-trusting results that aren’t very reliable.”

Related article from Houston Methodist Hospital (2024): Should You Do a Gut Microbiome Test? Key point: “While these tests seem to be effective in mapping the gut microbiome, there is currently no benchmark for what a ‘normal’ gut microbiome looks like. So the question becomes what to do with the results…microbiomes are highly variable — even normal, healthy ones. This makes it incredibly challenging to define the patterns or signatures that suggest a microbiome has become imbalanced. Plus, the at-home steps for correcting microbiome imbalance aren’t established either.”

My take: It is uncomfortable informing families that these gut microbiome tests have little clinical value because there is not a proper way to interpret the results. In addition, this study shows that the tests from one place to another produce wildly different results.

While one’s microbiome is important, we still don’t understand what exactly is a normal microbiome.

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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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How Long Should a pH Probe Last to Accurately Diagnose Gastroesophageal Reflux

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RI Rusu et al. Clin Gastroenterol Hepatol 2026; 24: 365-374. Open Access! The Optimal Duration of pH Monitoring: Testing the Validity of Lyon 2.0 Recommendations for Wireless pH Measurement

Background: “The Lyon 2.0 consensus recommends 96-hour wireless pH studies for gastroesophageal reflux disease (GERD) diagnosis…Ninety-six-hour monitoring is not always possible, either for technical reasons (eg, early detachment of the pH sensor) or for practical and financial reasons (48-hour studies are routine and cost-efficient in many centers).”

Methods: Data from 944 patients (16-85 years) with 4-day recordings (Bravo capsule) was reviewed. Patients were classified at 24, 48, and 72 hours against the 96-hour reference standard. Acid exposure time (AET) <4% was conclusively negative, and AET >6% was conclusively positive for GERD.

Key findings:

  • With longer duration, more patients were able to be diagnosed with GERD and fewer patients were in the indeterminate group. The proportion of patients with inconclusive results (AET 4%–6%) reduced from 113 of 944 at 24 hours to 40 of 113 at 96 hours (35% of subgroup; P = .02)
  • Only 3 of 60 patients with LA grade B esophagitis demonstrated physiologic reflux burden across all 96 hours of recording (which indicates that for significant reflux esophagitis, pH monitoring is not needed in most cases)
  • In the associated editorial (pg 306-308), the authors note that “the minimum duration for an effective study seems to be 3 days, because ~90% of conclusively positive studies identified over 4 days would be detected with 72 hours of recording. However, to achieve this, a 4-day study would need to be planned because of potential data loss, reported in almost a third of the cases in this and prior cohorts.”
  • “96-hour wireless monitoring is optimal for ruling out GERD when the pretest likelihood of reflux is low, especially when empiric PPI therapy is ineffective.”

My take: pH probe tests have many limitations. This study reinforces the need for longer studies in many patients when the findings would be equivocal with shorter duration studies.

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Prospective Study: Acute Gastroenteritis Increases Risk of Disorders of Gut-Brain Interaction

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A Palorath et al. Am J Gastroenterol 2026; 121: 242-247. Acute Gastroenteritis Is a Risk Factor for the Development of Disorders of Gut-Brain Interaction in Children

Methods:  A prospective, controlled, cohort study. Children (1-15 years) with recent AGE (cases) and siblings (controls) were followed for 6 months. We assessed DGBIs using a validated questionnaire (QPGS IV) per Rome criteria. Patients with underlying GI disorders (eg. Celiac, IBD, recent abdominal surgery) were excluded.

Key findings:

  • Among children without a history of DGBI before the AGE, 6 (12.2%) cases vs 0 control were diagnosed with DGBI (P = 0.01) at follow-up at 3 months
  • At 6 months, 5 cases (1 lost to follow-up) vs 0 control had persistent DGBI (P = 0.03)
  • Severity of AGE was correlated with PI-DGBI. Severe AGE included abdominal pain, ED consullt, and need for IV fluids

My take: It is well-known that previous AGE increases the risk of PI-DGBIs, especially irritable bowel syndrome. However, this is the first prospective cohort study showing this association between AGE and DGBIs in a nonoutbreak setting. In addition, it correlates the risk of DGBI with the severity of AGE.

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Oral Integrin Inhibitor for Moderate to Severe Ulcerative Colitis

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BE Sands et al. Clin Gastroenterol Hepatol 2026; 23: 525-534. Open Access! A Phase 2 Study of MORF-057, an Oral α4β7 Integrin Inhibitor in Moderately to Severely Active Ulcerative Colitis

Background: MORF-057 is an orally administered small-molecule drug that inhibits α4β7 integrin-mediated recruitment of α4β7-expressing lymphocytes to the gut. It has a similar target as vedolizumab, a monoclonal anti-integrin antibody used to treat ulcerative colitis (approved in 2014), but it requires parenteral administration.

Methods: This open-label, phase 2a, single-arm, multicenter trial (EMERALD-1) comprised a 6-week screening period, a 52-week active treatment period (including a 12-week induction period and 40-week maintenance period), and a 4-week safety follow-up period. Of the 35 participants enrolled in the main cohort, 18 participants received 100 mg of oral MORF-057 twice daily for the entire treatment period.

The primary efficacy endpoint was a change in the Robarts Histopathology
Index (RHI) score from baseline to week 12. “RHI was chosen as the primary efficacy assessment because it is an objective measure that can be assessed in a blinded fashion, which was critical given the open label study design. RHI also allows for a deeper, more quantitative probe than endoscopy.”

Key findings:

  • MORF-057 was well tolerated, and no treatment-emergent serious adverse events were
    observed
  • At week 12, participants (n= 35) exhibited a mean change from baseline in RHI
    score of ‒6.4 (standard deviation, 11.2). Additionally, 22.9% of participants (8/35) achieved
    RHI remission (RHI score ≤3)
  • In participants with evaluable data (n=18), the effects of MORF-057 on pharmacokinetics, pharmacodynamics, and clinical efficacy were achieved at week 12 and remained consistent to week 52
Symptomatic remission based on whether patient was advanced therapy (AT)-naive or AT-experienced

My take: This small open label study shows that an oral medication targeting α4β7 integrin has potential as an effective therapy for ulcerative colitis. If effective, then it would be important to understand how it compares to vedolizumab.

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Chronic Nonbacterial Osteomyelitis Associated with Pediatric Inflammatory Bowel Disease

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M Matar et al. J Pediatr Gastroenterol Nutr. 2026;82:487–494. Chronic nonbacterial osteomyelitis associated with pediatric inflammatory bowel disease: : A multicenter retrospective study from the Paediatric inflammatory bowel disease Porto Group of ESPGHAN

Methods: Retrospective study with 45 pediatric patients with inflammatory bowel disease (n=32 with Crohn’s disease, n=8 with ulcerative colitis, n=5 with IBD-U)

Key findings:

  • CNO presented in 15 patients (33%) within 3 months of IBD diagnosis, and in additional 20 (44%) patients after IBD diagnosis; in 10 (22%) patients CNO preceded the diagnosis of IBD with a median time 46 (25–248) weeks
  • 11 (24%) subjects displayed at least one additional extra-intestinal manifestations, including arthritis (6, 13%), erythema nodosum (4, 9%), sacro-ileitis (2, 4%), psoriasis (1, 2%), and pyoderma gangrenosum (1, 2%).
  • Complications occurred in six patients and included vertebral collapse, bone fracture, and bone deformity. In eight (18%) subjects vertebral collapse was present already at the time of diagnosis.
  • “While in most patients, diagnosis of CNO was associated with either clinical or laboratory indices of active IBD, especially CD, in some cases, the intestinal disease was quiescent.”
  • “All patients achieved remission of CNO at some point during follow-up, which may support the hypothesis that anti-TNF treatment is unlikely to promote CNO development and does not reinforce the theory of a paradoxical effect that has been suggested by Cordesse et al.22“

My take: This is a useful review highlighting the association of CNO with both active disease and quiescent IBD. The authors argue that their data does not support the development of CNO as a paradoxical effect. I disagree with this premise. Many of the extraintestinal manifestations, that anti-TNF agents can treat, rarely can be caused by them. Besides CNO, paradoxical reactions to anti-TNF agents have included the development of rheumatoid arthritis, psoriasis, hidradenitis suppurativa and autoimmune liver disease.

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