Category Archives: Gastroenterology

PODIUM Study: Jak Inhibitors and Ustekinumab Outperformed Vedolizumab as a 2nd Line Agent for Ulcerative Colitis

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G Privitera et al. Clin Gastroenterol Hepatl 2026; 24: 2539-2550. Open Access! Ustekinumab and Janus Kinase Inhibitors Outperform Vedolizumab as Second-Line Therapy in Anti-Tumor Necrosis Factor-Experienced Patients With Ulcerative Colitis

Before reading this article, I had to research why it was called “The Podium Study.” The research directly stacks three competing second-line classes of advanced therapies against each other: vedolizumab, ustekinumab, and JAK inhibitors; this is similar to a sports podium (1st, 2nd, and 3rd place), as the ultimate clinical goal of the study was to “rank” which medication performed best in terms of efficacy and safety after a patient fails anti-TNFα therapy. Of historical interest, there was an older, unrelated PODIUM trial, which stood for Pentasa Once Daily in Ulcerative Colitis for Maintenance of Remission.

Methods: In this retrospective, multicenter European study, there were 596 patients were included (301 vedolizumab, 149 ustekinumab, 146 JAKi) with a mean age of 43.9 ± 15.5 years.  JAKi included 114 with tofacitinib, 28 with upadacitinib, and 5 with filgotinib. Achievement of biochemical steroid-free clinical remission (SFCR) within 12 months was identified by having SFCR associated with biomarker normalization: FCP <250 μg/g or CRP <5 mg/L—if discordant, FCP was considered the reference biomarker.

Key findings:

  • Compared with vedolizumab, both ustekinumab and JAKi showed significantly higher probability of steroid-free clinical remission (SFCR) (aHR, 1.54 and aHR, 1.66, respectively) and biochemical SFCR (aHR, 2.26 and 3.37, respectively) at 12 months
  • The crude incidence rate of SFCR at 12 months was 65.3% for vedolizumab, 87.0% for ustekinumab, and 80.2% for JAKi.
  • From a safety standpoint, JAKi were associated with an approximately 4-fold increase in the incidence rate of treatment-related AEs—primarily infections—compared with both vedolizumab and ustekinumab.

Discussion Points:

“Optimal sequencing in UC after anti-TNF-α exposure remains an open issue, as direct comparisons are scarce. Overall, our findings are consistent with the network meta-analysis by Lasa et al, which reported superior efficacy of JAKi and ustekinumab compared with vedolizumab in inducing clinical remission and endoscopic improvement in anti-TNF-α-experienced patients.14 However, these conclusions derive from indirect comparisons across heterogeneous randomized trials.”

My take: Vedolizumab is a good choice as a 1st line agent for ulcerative colitis but has a lower success rate as a 2nd line agent. Also, this study likely underestimates the potential effectiveness of JAKi as most individuals received tofacitinib rather than upadacitinib.

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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.

AI for Capsule Endoscopy:

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D Fan et al. Clin Gastroenterol Hepatol 2026; 24: 2571-2583. Open Access! INTELCAPE: A Deep Learning-Powered System for Automated, High-Accuracy Crohn’s Disease Diagnosis via Capsule Endoscopy

Methods: In this retrospective, multi-center study with data from 2 Chinese hospitals, the authors developed artificial intelligence, INTELCAPE, for a multi-task deep learning system, to perform small-intestine segmentation, lesion detection, and CD diagnosis from full (capsule endoscopy) CE videos.

Key findings:

  • “INTELCAPE achieved state-of-the-art performance across all tasks.”
  • “For lesion detection, it achieved area under the curve values of 0.993 (Cohort 1) and 0.980 (Cohort 2), with 99.33% classification accuracy, which was comparable to that of specialists (97.83%) but superior to that of residents (91.05%; P < .001).”
  • “For CD diagnosis, INTELCAPE demonstrated robust generalizability, achieving area under the curve values of 0.982 (Cohort 1) and 0.984 (Cohort 2) with 90% diagnostic accuracy, comparable to that of specialists (93.33%) but 10-fold faster (P < .001).”
  • “INTELCAPE improved doctors’ diagnostic accuracy (76.7%–94.8%; P < .001), while reducing their interpretation time (67.9–22.5 minutes; P < .001).”

Discussion Points:

  • “CE generates thousands of images per examination, imposing a substantial analytical burden on clinicians. Manual analysis is labor-intensive and prone to human error, increasing the risk of missed lesions, particularly those with subtle appearances.”
  • “Real-world clinical workflows will require prospective validation on “all-comers” populations, robust handling of poor-quality videos, and device-specific fine-tuning.”

My take: Capsule endoscopy appears to be an ideal target for AI assistance. It has the potential to improve accuracy, reduce time, and augment the performance of less experienced clinicians.

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Flawed Dual Therapy Study of Vedolizumab and Upadacitinib

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J Yao et al. Clinical Gastroenterology and Hepatology, 2026. Combined Upadacitinib and Vedolizumab as 8-Week Induction Therapy for Moderate-to-Severe Ulcerative Colitis: A Multicenter, Randomized Controlled Trial

Many patients do not respond to current advanced therapies which have prompted evaluation of dual therapy regimens. In this randomized open-label trial, the authors compared upadacitinib-vedolizumab dual therapy against vedolizumab monotherapy (40 combination, 73 monotherapy) for moderate-to-severe ulcerative colitis. Upadacitinib was dosed at 45 mg per day.

Key findings:

  • Endoscopic remission at week 8 was achieved by 37.5% in the dual therapy group compared to 15.1% with vedolizumab monotherapy (adjusted odds ratio, 3.34, 1.34–8.58; P = .010)
  • Clinical remission (65.0% vs 35.6%; P = .002) was significantly higher with combination therapy.
  • Adverse event rates were comparable (7.5% vs 6.8%), with no serious adverse events.

It is great to see more dual therapy data . While I am a little reluctant to criticize this study, as I think this type or research is both important and difficult, this trial has a couple problems. First of all, vedolizumab monotherapy may take twice as long to become effective; as such, the results at week 8 in isolation provoke more questions than answers. In addition, at this time point, it is not clear if combination therapy would be more effective than upadacitinib monotherapy.

In their discussion, the authors state that “the 65.0% clinical remission rate at week 8 substantially exceeds rates reported in pivotal induction trials for either upadacitinib (up to 34%11,25) or vedolizumab (approximately 17%24) as monotherapy….. The absence of a upadacitinib monotherapy arm precludes formal assessment of synergy; however, the observed combination endoscopic remission rate (37.5%) exceeds published upadacitinib monotherapy rates for Mayo score = 0 (approximately 14%–18%),11 suggesting a benefit beyond that of upadacitinib monotherapy alone.” However, in a study (RS Dalal et al. Clin Gastroenterol Hepatol 2024; 22: 666-668) comparing monotherapy with upadacitinib versus ustekinumab, upadacitinib had a steroid-free clinical remission rate of 62.1 %, and an endoscopic remission 37.5%. These results are nearly identical to the results of the combination therapy group.

My take: This study shows that upadacitinib works quicker than vedolizumab for moderate-to severe UC. It does not prove that upadacitinib in combination with vedolizumab is more effective than upadacitinib monotherapy.

The anticipated followup data at 1 year will be helpful to determine whether the combination with vedolizumab impacts long-term effectiveness of upadacitinib monotherapy. It is unfortunate that an upadacitinib monotherapy arm was not included in this study.

Another useful study would be whether patients who respond to upadacitinib as an induction combination therapy with vedolizumab could transition to vedolizumab monotherapy. This would leverage upadacitinib’s rapid onset and if effective, allow long-term treatment with vedolizumab which is considered to have the most favorable long-term safety data.

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The Tricky Problem of IBD with IBS-like symptoms

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Ma C, Ford A, Hashash J et al. Gastroenterology, 2026; 171, 504-520. Open Access! Recommendations for the Evaluation and Management of Inflammatory Bowel Disease With Irritable Bowel Syndrome–Like Symptoms: A Joint Rome Foundation and International Organization for the Study of IBD (IOIBD) Consensus

Background:

  • “A substantial proportion of persons with inflammatory bowel disease (IBD) in remission continue to experience abdominal pain, altered bowel habits, and bloating that resemble irritable bowel syndrome (IBS). Lack of standardized definitions and evidence-based management strategies leads to diagnostic ambiguity and potentially unnecessary escalation of IBD therapy. A joint Rome Foundation/International Organization for the Study of Inflammatory Bowel Disease Working Team developed consensus recommendations on nomenclature, evaluation, and treatment of IBD with IBS-like symptoms.”
  • “A meta-analysis of 27 studies demonstrated that 1 in 3 individuals with IBD reported
    coexisting IBS, although estimates were heterogeneous and few studies objectively excluded active disease (11.2% to 63.6%).[1] Among those with endoscopic or histologic
    remission, 1 in 4 reported IBS-like symptoms.”

Methods: A multidisciplinary international panel applied a modified RAND/UCLA Appropriateness Method and determined recommendations for evaluation and management of these patients.

Terminology:

  • “The preferred term was “IBD with IBS-like symptoms,” defined as abdominal pain, bowel habit change, and/or bloating not explained by active inflammation or structural disease.”

Pathophysiology:

Evaluation to determine whether GI symptoms are related to IBD or are related to IBS-like symptoms

Key points:

  • “An FC [fecal calprotectin] below 150 μg/g is considered normal, but persons with IBD with ongoing symptoms may require endoscopic evaluation even with a normal FC, especially in the setting of small bowel involvement or after surgery in CD.”
  • “In clinical care, the diagnosis of IBD with IBS-like symptoms can be supported using the Rome Clinical Diagnostic Criteria (having symptoms sufficiently bothersome to seek health care for at least the prior 8 weeks or when other conditions have been excluded).”
  • Dietary treatments of IBS symptoms were recommended including psyllium and a trial of a low FODMAP diet.
  • Medication treatments of IBS symptoms were recommended including TCAs, SSRIs, SNRIs, antidiarrheals (e.g. loperamide), antispasmotics, peppermint oil, osmotic laxatives, 5-HT4 receptor agonists and secretagogues (e.g. linaclotide).
  • Behavior therapies including GI-focused cognitive behavioral therapy and gut-directed hypnotherapy were recommended
Treatment algorithm

My take: Overall, this expert panel endorsed a broad-range of current IBS treatments for patients with well-controlled IBD experiencing ongoing GI distress. This paper focuses attention to this difficult clinical problem in which many patients, historically, have received escalating IBD therapy rather than IBS therapies. Part of the problem is that it is difficult to be certain that a patient’s IBD is well-controlled and that there are no structural problems (e.g. strictures). In addition, many patients have very mild findings and it can be hard to know if these findings are enough to account for the symptoms. The opposite problem can also occur in which patients have very active IBD yet have few clinical complaints.

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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.

AI Diagnosis of Achalasia on Plain Chest X-ray

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T Ochaiai et al. Clin Gastroenterol Hepatol 2026; 24: 2308-2310. Open Access! Artificial Intelligence-Based Detection of Achalasia on Plain Chest Radiography

Methods: This retrospective study collected posteroanterior plain chest radiographs of
patients with and without achalasia. The training and validation datasets comprised 447
chest radiographs taken between January 2017 and March 2023.

Key findings:

  • In the validation dataset, the area under the curve for identifying achalasia was 0.971, and using Youden’s index, the sensitivity, specificity, accuracy, and positive and negative predictive values were 0.950, 0.917, 0.932, 0.905, and 0.957, respectively
  • In the temporal test dataset, the area under the curve for detecting achalasia was 0.964, and using Youden’s index, the sensitivity, specificity, accuracy, and positive and negative predictive values were 0.941, 0.891 , 0.901, 0.696 , and 0.983, respectively.
In Figure F, the CXR corresponds to the findings in the barium esophagogram in G

Discussion:

  • It may help detect patients with early achalasia with mild symptoms who are unlikely to undergo EGD. However, the rarity of the condition may result in many false positives.

My take: In this cohort, AI was developed and validated to detect achalasia on chest radiographs. This is yet another example of how AI can yield additional information from routine testing. Previously, AI has been shown to potentially identify diabetes from routine CXR (Emory News 2023: AI model enables earlier detection of diabetes through chest x-rays).

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Helicobacter pylori Treatment 2026

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T Rokkas, DY Graham. Gastroenterol 2026; 171: 271-284. The Unfinished Agenda in Helicobacter pylori Treatment: Resistance, Microbiome Effects, and Future Directions

This was a narrative review aimed at synthesizing contemporary evidence.

Background: Globally, approximately half of the population is infected. Prevalence surpasses 70% in many low- and middle-income countries (LMICs) where crowded living conditions, poor sanitation, and limited access to clean water enhance transmission. 

Key points:

  • Global resistance to clarithromycin, metronidazole, and fluoroquinolones significantly undermines the performance of traditionally effective antimicrobial therapies. The corner stone of successful antimicrobial therapy is susceptibility-guided therapy but remains of limited use with H pylori because of lack of infrastructure.
  • Clarithromycin should no longer be prescribed as an empiric therapy (ie, it should be restricted to susceptibly based therapy)…Despite the poor cure rates with clarithromycin achieved with vonoprazan in the United States, the American College of Gastroenterology H pylori guideline still recommended vonoprazan triple therapy.17 (With clarithromycin-susceptible infections, vonoprazan is not more effective than PPIs.) The discordance between guideline recommendations and clinical effectiveness contributes to treatment failures.
  • Bismuth quadruple therapy (BQT), which combines metronidazole with tetracycline and bismuth, can partially overcome moderate metronidazole resistance through antimicrobial synergy and higher effective dosing.
  • Next-generation sequencing (NGS) is now available at a fraction of the cost of an endoscopy in the United States using stools, fresh, frozen, or paraffin-embedded gastric biopsies37 (American Molecular). Economic analyses indicate that susceptibility-guided therapy is cost-effective.
  • When BQT fails or is unavailable, several alternative regimens can be considered.4–6 Rifabutin-based triple therapy can achieve eradication rates of 70% to 90% even in heavily pretreated patients.40
  • When designing rescue therapy, antibiotics previously associated with failure should not be reused unless susceptibility has been clearly established.
  • Optimizing H pylori treatment requires evidence-based regimen selection, precision-guided strategies, antimicrobial stewardship, and equitable access to essential medications

My take: This is a helpful review of H pylori issues and management.

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Should the Gluten Threshold Dose in Celiac Disease Change Based on Immune Activation?

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Background: Interleukin 2 (IL2) rises acutely after gluten ingestion, allowing the definition of threshold doses that trigger immune activation.

Methods: This was a randomized double-blind, placebo-controlled adaptive dose–response trial in adults with biopsy-proven celiac disease on a gluten-free diet for >2 years. Participants (n = 51; median age, 52 years; 69% were female) underwent 3 oral gluten (1–1000 mg) or placebo challenges at 4-week intervals. Eliciting dose (EDp, ie, the dose at which p% of people respond) was estimated by interval-censored survival analysis.

Key findings:

  • Gluten induced dose-dependent IL2 elevations, with ≥2-fold increases in 83% at 1000 mg, 83% at 610 mg, 36% at 90 mg, 17% at 13 mg, 27% at 8 mg, and 17% at 3 mg; none responded to 5 mg, 2 mg, 1 mg, or placebo.  
  • Estimated ED50 was 111 mg, ED10 was 2.4 mg, ED05 was 0.8 mg, and ED01 was 0.1 mg

From the editorial:

“To date, the few investigators who addressed this question defined tolerance in relation to quantifiable histologic damage (intestinal morphometry)…Bearing in mind that the typical Western diet contains 10–15 g of gluten per day, these studies found that the protracted, daily ingestion of 1000, 200, or 50 mg of gluten elicits significant damage at the mucosal level.2,3 A daily dose of 10 mg was also associated with minimal architectural changes in some patients…

In 2007, the Food and Agricultural Organization/World Health Organization Codex Alimentarius Commission4 applied these findings to establish that commercially available gluten-free food must not contain more than 20 mg/kg gluten (20 part per million [ppm]), as this would ensure that daily gluten intake does not exceed 10 mg…Not a single case of proven intolerance to 20 ppm gluten-free food has been described…in some 20-ppm countries, most labeled gluten-free products already contain much less than 20 ppm of gluten, usually <10 ppm5…

The authors concluded that the daily gluten threshold should be decreased because acute IL2 release occurred at 3 mg, which is less than is allowed by current food-labeling rules for gluten-free products…

Because symptoms did not correlate with the result of the IL2 test for gluten doses <1 g, further prolonged microchallenge studies remain the only reliable strategy to investigate the correlation between the IL2 test and the gold standard of CeD activity—histologic damage of the small intestinal mucosa.10,11“

My take: This study is intriguing that there is evidence of immune activation at lower gluten exposures; however, it does not prove that changing the gluten threshold is beneficial.

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Singing Therapy for Supragastric Belching

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H Shang H et al. Clinical Gastroenterology and Hepatology, 2026; Singing Therapy versus Diaphragmatic Breathing for Supragastric Belching: A Multicenter Randomized Controlled Trial

Background: “Supragastric belching (SGB) significantly impairs quality of life. Although diaphragmatic breathing is recommended as a first-line intervention in clinical guidelines, some patients perceive it as monotonous.”

Methods: “This randomized controlled trial, 72 adult patients with supragastric belching diagnosed according to Rome IV criteria were randomly assigned (1:1) to structured singing therapy (ST) or diaphragmatic breathing at 2 tertiary gastroenterology centers in China.  The primary outcome was the treatment response, defined as ≥50% reduction in belching visual analog scale scores.”

Singing Therapy:

“Patients with excessive belching episodes underwent structured ST sessions administered by gastroenterologists using 1 of 4 standardized Chinese folk songs (“The Sea,” “For Whom,” “Story of Spring,” or “The Most Dazzling National Style”), with each session lasting approximately 5 minutes.

Participants were required to:

  1. Perform vocalization with musical accompaniment.
  2. Sustain open-mouth phonation to promote diaphragmatic activation, with real-time feedback provided via ‌visual cues‌ (observation of abdominal expansion in a mirror during inhalation) and tactile cues (light hand placement on the abdomen to monitor respiratory motion and suppress thoracic dominance).
  3. Achieve a target vocal intensity of 80 dB, verified using calibrated smartphone decibel meter applications (Decibel Meter App).
  4. Patients were instructed to perform 5-minute vocal therapy sessions 3 times daily, with additional 5-minute sessions when symptomatic. This regimen was maintained continuously for 7 days.”

Key Findings:

  • “After 1 week, ST demonstrated a significantly higher response rate than diaphragmatic breathing both immediately postintervention (72.2% vs 38.9%; P = .004) and at 1-month follow-up (50.0% vs 30.6%; P = .032). “
  • “ST demonstrated greater and more sustained benefits in quality-of-life measures.”

Discussion:

  • “ST may ameliorate belching through mechanisms potentially shared with DB. First, both interventions likely reduce belching by attentional diversion, as distraction-based attentional modulation has been shown to alleviate belching.21“
  • “Existing literature indicates that both ST16,28 and DB29 possess anxiolytic effects.”

My take: It will be interesting to see if this therapy will be effective in different populations and in pediatric cohorts. Also, could this treatment lead to more American Idol auditions?

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Two pictures of the exterior and interior of the Harpa Opera house in Reykjavkik. The irregular, crystalline shapes mimic the geometric basalt columns found in volcanic rock across Iceland.

Discordant Clostridiodes difficile Testing In Patients with Inflammatory Bowel Disease

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P Ramakrishan et al. Inflamm Bowel Dis 2026; 32: 1313–1320. Discordant Clostridioides difficile testing as a predictor of inflammatory bowel disease therapy escalation

Background: “In the general population, individuals with discordant tests (PCR+/TOX−) have similar outcomes to PCR− individuals, suggesting that this group represents individuals colonized with C. difficile.[14]”

Methods: In this retrospective study (n=117), outcomes assessed included CDI-directed therapy or escalation of IBD treatment.

Key findings:

  • 79% (93/117) were PCR+/TOX− and 21% (24/117) were PCR+/TOX+
  • PCR+/TOX+ patients had significantly higher CRP (98 vs 6 mg/L, P = .005)
  • PCR+/TOX− patients had more severe underlying IBD and higher rates of steroid use (48% vs 21%, P = .02) and were significantly more likely to require IBD therapy escalation (54% vs 25%, P = .004). Multivariable analysis showed PCR+/TOX− status (odds ratio [OR], 3.2) was a significant predictor of IBD treatment escalation. Antibiotic use did not significantly alter the need for escalation among PCR+/TOX−  patients.

Discussion:

  • “Most IBD patients who are PCR+/TOX−  are colonized with C. difficile, and IBD treatment could be considered rather than delaying for CDI therapy.”

My take: In patients with IBD, PCR-positivity for C diff is frequently a false positive due to high rates of colonization in this population. Patients who have their infection confirmed with an immunoassay are much more likely to respond to C diff therapy.

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Resources:

National Civil Rights Museum in Atlanta, GA. One of the powerful exhibits is a Woolworth lunch counter replica with headphones.  With your eyes closed, the exhibit challenges you to keep your hands on the counter as one receives menacing threats like ‘Boy, I’m going to kill you.’ 

Dupilumab for Eosinophilic Gastritis: DEGAS study

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N Gonsalves, E Dellon E, K Kliewer K et al. The Lancet Gastroenterology & Hepatology, 2026; DOI: 10.1016/S2468-1253(26)00116-0. Open Access! Dupilumab versus placebo in adults and adolescents with eosinophilic gastritis (DEGAS): a double-blind, placebo-controlled, phase 2, multicentre, randomised controlled trial

Methods: This was a phase 2b trial with a 12-week, double-blind, placebo-controlled period, followed by a 24-week open-label extension period. Patients aged 12–70 years from 11 hospitals in the USA with histologically active eosinophilic gastritis (≥30 eosinophils per high-power field [HPF] in at least five HPFs in the gastric antrum and/or body) and moderate-to-severe symptoms. Eligible patients were individually randomised (1:1) to parallel groups and received six injections over 12 weeks: subcutaneous dupilumab (n=21) (600 mg once followed by 300 mg every 2 weeks) or subcutaneous placebo (n=20).  The primary endpoint of relative change from baseline in mean gastric eosinophil count.

Key findings:

  • At week 12, the relative reduction in the primary endpoint was greater with dupilumab (estimated mean change –50%) than with placebo (–4%)
  • Reduction from baseline in EoG-REFS (Eosinophilic Gastritis Endoscopic Reference Score) at week 12 was greater with dupilumab (estimated mean change –3·47 points than with placebo (–0·06 points)

 

 

Discussion Points:

“Currently, there are no FDA-approved therapies for patients with eosinophilic gastritis…this first prospective trial of dupilumab for eosinophilic gastritis show a greater reduction in mean gastric eosinophil count from the five most eosinophil-dense HPFs (the primary endpoint) with dupilumab compared with placebo.”

My take: Dupilumab improved eosinophilic gastritis histology and endoscopic appearance. This study suggests that there may be overlapping pathophysiology between eosinophilic gastritis and eosinophilic esophagits as dupilumab appers to be effective in both disorders.

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