Comparing Vedolizumab in “Early” and “Late” Crohn’s Disease

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Lancet Gastroenterol Hepatol 2026; 11: 12-21. Vedolizumab in early and late Crohn’s disease (LOVE-CD): a phase 4 open-label cohort study

Methods: Eligible patients were adults aged 18–80 years with moderate to severe Crohn’s disease (Crohn’s Disease Activity Index [CDAI] 220–450, with ulcers at endoscopy). Patients were divided into two groups: those with early Crohn’s disease, n=86 (defined as a diagnosis less than 2 years ago and naive to advanced treatment [naive or only treated with corticosteroids or immunomodulators, or both]); and those with late Crohn’s disease, n=174 (defined as a diagnosis more than 2 years ago and previously treated with corticosteroids, immunomodulators, and anti-TNF agents). The primary endpoint was the proportion of patients with clinical and endoscopic remission (defined as CDAI ≤150 and SES-CD <4) at both week 26 and 52.

Key findings:

  • Clinical and endoscopic remission at both week 26 and 52 was achieved in 27 (31·4%) of 86 patients with early Crohn’s disease versus 15 (8·6%) of 174 patients with late Crohn’s disease (difference 22·8%, 95% CI 12·6–33·7)
  • Serious adverse events occurred in three (3·5%) of 86 patients with early Crohn’s disease versus 46 (26·4%) of 174 patients with late Crohn’s disease and included infections (one [1·2%] vs 13 [7·5%]), surgery (none vs eight [4·6%]), intestinal obstruction (none vs four [2·3%]), exacerbation of Crohn’s disease (one [1·2%] vs six [3·4%]), and malignancy (none vs three [1·7%])
Corticosteroidfree clinical remission at all timepoints

Discussion:

  • “After 52 weeks of open-label treatment, almost 60% of patients with early disease achieved clinical remission and more than 50% were in endoscopic remission. By contrast, deep remission rates at both weeks 26 and 52 were observed in less than 10% of patients with late Crohn’s disease (ie, those with longstanding disease and previous exposure to anti-TNF
    agents).”
  • “Despite the earlier stage at which vedolizumab was initiated, disease severity was comparable betweenthe early and late Crohn’s disease groups, from a clinical (median CDAI 255 vs 259), endoscopic (median SES-CD 9 vs 12), and biochemical perspective (median serum C-reactive protein 9 mg/L vs 8 mg/L).”
  • “A pivotal observation in LOVE-CD was that dose intensification after week 26 (ie, doubling the dose) in patients without an endoscopic response did not lead to higher endoscopic remission rates, despite significantly higher serum vedolizumab concentrations. This
    finding suggests that the dosing schedule that was originally designed and approved is optimal for most patients and saturates the target. Patients who do not respond most likely have other dominant immune pathways that are activated and remain unaffected by
    vedolizumab.”
  • “All three classes of biologics approved for the treatment of Crohn’s disease perform better when initiated early in the disease course.”

My take: For Crohn’s disease (CD), vedolizumab should be mainly used in those without prior biologic therapy. In addition, changes in vedolizumab dosing based on concentrations is much less helpful than it is with anti-TNF agents.

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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.

What’s Changing For the GI Tract in Patients with Cystic Fibrosis Due to Highly Effective Modulator Therapy

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P Saikumar et al. Am J Gastroenterol 2026; 121: 103-111. A Comprehensive Review of Gastrointestinal Manifestations in Cystic Fibrosis in the Era of Highly Effective Modulator Therapy

Thanks to Ben Gold for sharing this article.

Exoocrine Pancreatic Insufficiency (EPI)

  • “Mutlicenter studies, KIWI and ARRIVAL, demonstrated increase in FE-1 (fecal elastse-1) after treatment with ivacaftor, signifying improvement in in pancreatic function”
  • “The PROMISE study, a large 56-center prospective observational study with participants at least 12 years of age…found ETI (Elexacaftor-tezcaftor-ivacaftor) did not result in improvement in pancreatic function…raises the question if age of initiation of CFTR modular therapy has an influence in recovery of pancreatic function.”

Acute Pancreatitis

  • “With the improvement in pancreatic function seen in some patients with CF on HEMT, there have been emerging reports of acute pancreatitis.”

CF Hepatobiliary Involvement

  • “Previously referred to as CF liver disease (CFLD), hepatobiliary complications in CF are now recommended to be classified as CF hepatobiliary involvement (CFHBI) or advanced CFLD”
  • “Vigilant monitoring of transaminase levels and liver function is crucial after CFTR modulator initiation, because drug-induced liver injury (DILI) is a potential concern with elexacaftor/tezacaftor/ivacaftor (ETI) therapy…A disproportionality analysis of Food and Drug Administration adverse event reporting system data from 2019 to 2022 identified 452 reports of DILI associated with ETI use, demonstrating a statistically significant association”
  • “ETI is not recommended for those with Child Pugh Classification C and dose reduction is recommended for Child Pugh classification B in clinically appropriate situation when benefit outweighs the risk”

Nutrition

  • “In addition to macronutrient deficiency, Children with Cystic Fibrosis are at risk of deficiencies in fat-soluble vitamins, minerals, and essential fatty acids (38). With an overt focus on nutrition, PERT, and advancements in CFTR modulators, an opposite trend is now being seen, with a higher incidence of obesity and overweight in this population…[and] associated comorbidities such as coronary heart disease, metabolic dysfunction-associated steatotic liver disease, and metabolic syndrome-including hyperlipidemia and diabetes.”

Eating Disorder

  • “Disordered eating is relatively a new concern in this population. There are controversial data on the prevalence of eating disorder in PwCF” (people with CF).”

GERD

  • “Data indicate that children with CF are 4 times more likely to experience acid gastroesophageal reflux than the general population (59)…RECOVER, a multicenter study of ETI in PwCF displayed decreased GI symptoms, including GERD, after 12 months of treatment (61). Similarly, treatment with IVA was associated with symptomatic relief of GERD at 52 weeks and also showed a decline in extraesophageal reflux in PwCF treated with
  • IVA for 12 months (62).”

Meconium Ileus

  • Recent case reports, “although differing in ETI initiation timing, outcome severity, suggest that prenatal ETI exposure may positively influence MI (69).”

Constipation

  • “There are limited data regarding the effect of ETI on constipation, asthe PROMISE trialshowed only small improvements in Patient Assessment of Constipation-Symptoms score and Patient Assessment of Constipation-Quality of Life”

DIOS

  • “There is paucity of data describing impact of HEMT [highly effective modulator therapry] on DIOS. By correcting the CFTR dysfunction, HEMT may help reset the ion/fluid balance which is considered one of the main factors in pathogenesis of DIOS.”

My take: “CFTR modulators have revolutionized the management of CF by dramatically altering the course of the disease and improving patient outcomes.” They are also altering the clinical GI manifestations.

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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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Highway to El Chalten and Mount Fitz Roy, Argentina

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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