How Effective is Ustekinumab Dose Intensification in Crohn’s Disease: REScUE Trial

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Methods: This was an investigator-initiated, multicenter, randomized, placebo-controlled trial conducted at 15 hospitals in Belgium. Eligible patients were adults (n=108) with CD treated with ustekinumab on maintenance dosing of 90 mg subcutaneous every 8 weeks and experiencing a secondary loss of response. Patients were randomized 1:1 to receiving a single intravenous reinduction with ustekinumab ≈6 mg/kg followed by either subcutaneous ustekinumab 90 mg every 4 weeks or every 8 weeks until week 48. 

Key findings:

  • Steroid-free clinical remission at week 48 was reached in 15% vs 19% of patients in the every 4 weeks vs the every 8 weeks group 

Discussion Points:

  • “Remarkably, the overall steroid-free clinical remission rates at week 48 were low in both arms: 15% and 19% for ustekinumab Q4W and Q8W, respectively. Most of the patients achieved clinical remission in the first 24 weeks after IV reinduction though, suggesting that the IV reinduction is the main driver of the effectiveness, rather than the subsequent SC dose intensification.”
  • “Our results are in contrast with several retrospective and observational nonrandomized and open-label cohort studies suggesting a clinical response rate after dose intensification up to 60% and clinical remission rates up to 50% after 1 year of treatment.4,13–17“

The associated editorial notes that the modest remission rate could be partly due to a more refractory patient poulation. “The cohort was indeed difficult to treat: median disease duration exceeded a decade, and more than 90% of patients had prior anti–tumor necrosis factor exposure.” Despite this caveat, “the trial avoids overestimating therapeutic success and aligns outcomes with contemporary treat-to-target principles.4 From this perspective, REScUE provides a realistic benchmark for what ustekinumab intensification can and cannot achieve in routine clinical practice.”

The editorial also notes that the “STARDUST trial [which] evaluated a treat-to-target, endoscopy-guided escalation algorithm vs standard of care in ustekinumab-treated CD and did not demonstrate a clear advantage for the intensive, endoscopy-driven strategy at 1 year.7“

My take (borrowed from editorial): “In carefully selected patients who previously responded well to ustekinumab, a short and closely monitored trial of IV reinduction may be considered. However, the threshold for switching to another advanced therapy should remain low if treatment targets are not achieved.”

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This year’s Peachtree Road Race. It didn’t look like I would be finishing first this year!

Does Isolated Ulcerative Proctitis Increase the Risk of Rectal Cancer?

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AH Everhov et al. Gastroenterol 2026; 171: 158-160. Open Access! Incidence of Rectal Cancer in Patients With Isolated Ulcerative Proctitis: A Population-Based Cohort Study

Methods: Using a prospective nationwide registry (SWIBREG) (1997-2023), there were 15,957 individuals diagnosed with isolated proctitis and matched to 158,079 population comparators. Median followup for patients with isolated proctitis was 10.8 years.

Key findings:

  • Rectal cancer incidence was 0.11% in patients and 0.09% in comparators at 5 years and 0.16% and 0.21%, at 10 years.
  • During follow-up, inflammation remained limited to the rectum in 60% of patients, whereas 23% developed left-sided colitis and 17% developed extensive colitis

Discussion Points:

  • “Results from this nationwide study indicate patients with isolated proctitis have no elevated rectal cancer risk with respect to the general population.”
  • “40% of patients experienced disease extension” which is similar to prior studies.
  • “European (European Crohn’s and Colitis Organisation)9 and US (American College of Gastroenterology)10 guidelines endorse standard population screening in limited-extent disease, and our data support these recommendations.”

My take: This should provide a lot of reassurance for our patients with isolated proctitis.

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Camp Weekaneatit 2026

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Last Sunday, along with my colleagues, Jeff Lewis, and Nirav Patel, I helped check in kids for Camp Weekaneeatit! (glutenfreecamp.org). This is a gluten-free camp for youth with ​Celiac Disease and ​Gluten Intolerance. This year’s staff shirt was “S’more Fun Without Gluten;” though, I elected to wear my T-shirt from 2018.

The camp was started more than 15 years ago by my partners, Dr. Jeff Lewis and Dr. Bill Meyers.

The camp is located just north of Atlanta at Ft Yargo (Winder, Georgia). The ~125 participants come from all over the U.S including Texas, Michigan, Ohio, Massachusetts, Colorado, Arizona, Florida, South Carolina, and Alabama. There was one kid, whose father is a marine, who flew in from Japan!

Most of the campers have come several times and have had a great experience. Here is an excerpt from a letter from a camper’s parent:

“My daughter was at camp with you this summer.  I can’t tell you how much fun she had.  She was diagnosed with celiac when she was just 2, so she has never known a world where she could just relax and be like everybody else.  Camp gave her so much freedom, and she grew so much in just one week.  Today is her birthday and her first day of school.  Her camp friends have already texted to wish her happy birthday!…This is the first time she has had friends with celiac disease — I can only imagine how much more supported that makes her feel…  I asked her what it was like to not have to ask a million questions before every bite she ate.  She said, “I felt like I didn’t even have celiac disease all week. I felt like a normal person.” 

Last year enrollment started in the middle of November for summer 2026. Space is limited!

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Eosinophilic Esophagitis: Aerodigestive Disease Perspective

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TA Temtem, K Liu, KL Kennedy, BD Gold. Pediatr Gastroenterol Nutr. 2026; Online ahead of print. Eosinophilic esophagitis: An aerodigestive perspective

This review article highlights the management and high frequency of eosinophilic esophagitis in children with complex aerodigestive disease disorders. Congratulations to my colleague Dr. Benjamin Gold, one of the contributors, and our aerodigestive disease team for this publication.

Key points:

  • “Special populations such as esophageal atresia/tracheoesophageal fistula and those patients requiring laryngotracheal reconstruction (LTR) should undergo esophagogastroduodenoscopy with biopsies to evaluate for EoE, even in absence of typical symptoms”
  • “The prevalence of EoE in aerodigestive patients ranges from 3.7% to 25% (Table 1).”
  • “The clinical presentation of EoE can range from typical symptoms of feeding difficulty to atypical presentations of chronic cough, recurrent croup, hoarseness, or inflammatory consequences found at the time of airway evaluation.3, 4, 12“
  • Delays in the diagnosis of EoE for 6 years or more are common. “Studies demonstrate…a 9% increased risk of stricture for each additional year of undiagnosed EoE.”
  • “Patients undergoing LTR are also managed by aerodigestive teams and should have screening esophagogastroduodenoscopy (EGD) prior to surgery, as untreated EoE can result in graft failure.10“
  • “Management of aerodigestive patients with EoE is similar to the general population…A limitation of topical steroids is that oral is the only route of administration.”

Critique:

  • The authors note that “in a review of 251 EoE patients, 14% of the patients who were initially evaluated by otolaryngology presented with isolated airway complaints and an absence of GI symptoms.14” However, in my experience, many ENT physicians are not asking questions like ‘how long does it take your child to eat? or ‘does your child need to drink a lot of fluid to help them swallow?’
  • The authors conclude that “it is imperative for the aerodigestive clinician to recognize the range of EoE presentations and thus, with a higher index of suspicion, reduce diagnostic delay. EA/TEF patients are at high risk of EoE and should undergo routine surveillance EGD, even in the absence of symptoms.” In my experience, the threshold for arranging a triple endoscopy is quite low for the aerodigestive team. This messaging​, though, is important for patients seen outside the aerodigestive clinic.
  • There is no discussion of cost and redundancy in this article. Many aerodigestive patients, prior to going to the multispecialty clinics, already have GI, pulmonary and/or ENT physicians. Communication among their specialists could obviate the need for aerodigestive evaluation in many patients.

My take: This article provides a useful review of EoE in the aerodigestive disease population and highlights how respiratory symptoms can be the main clinical presentation.

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Atlanta Botanical Gardens

Extending Benjamin Franklin’s Observations: Chart Your Fart Study

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E Brindal et al. JAMA Netw Open. 2026;9;5):e2615637. doi:10.1001/jamanetworkopen.2026. 15637. Open Access! Regular Flatulence Patterns Among Community-Dwelling Individuals in Australia. Thanks to Stan Cohen for sharing this study.

Methods: Cross-sectional study with 6416 participants  Data were recorded into a purpose-designed mobile phone application (Chart Your Fart) by participants who logged their flatus passages in real time, consistent with experience sampling methods.3

Key findings:

  • See Table below – Mean flatus per day was 5.0

Discussion:

  • “In terms of range, observed data suggest good consistency with other methods, including retrospective frequency reports in a large US sample of individuals experiencing gas or bloating (n = 16 537),6 a small laboratory study that collected a median of 8 emissions throughout 24 hours,7 and even Benjamin Franklin’s personal account of “discharging wind from bowels” 7 times a day.8“
  • “Limitations of this study include failing to quantify emissions made while asleep due to reliance on self-report.”

My take: Looks like another good study to discuss at the GI dinner table. Also, lots of jokes that would be apropos. Here’s one:

An elderly patient goes to her doctor and at the end of her exam she tells him there is one other matter that she would like to discuss. “It seems that I have frequent gas but fortunately it is silent and does not smell. I have even passed some gas while I’ve been here.” The physician says, “Hmmm… take these pills for one week and then come back.”

When she returns, she complains, “I don’t know what was in those pills. The gas now smells terrible but thank goodness it is silent.” The doctor replies, “Well, it looks like the antibiotics have improved your ability to smell. Now we need to get your hearing evaluated.”

Related blog post: Somewhat Funny Flatulent Research

Island Ford, Sandy Springs at sunrise

Safety Data Up to Seven Years with Vedolizumab

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E Louis et al. Clin Gastroenterol Hepatol 2026; 24: 1654-1665. Open Access! Long-Term Safety of Vedolizumab in Patients With Ulcerative Colitis/Crohn’s Disease: A Prospective Observational Study

Methods: This was a prospective, observational, multicenter cohort study in adult patients (n=5208) with UC or CD starting treatment with vedolizumab or other biologics. The primary safety outcome was serious infections compared between cohorts using a Cox proportional hazards model adjusted by propensity score. Clinical effectiveness was a secondary outcome. Mean follow-up duration was 37.4 months. The vedolizumab group had greater age, duration of disease, and concomitant medication use at baseline, indicating more advanced disease.

Key findings:

  • In patients with UC, the incidence rate per 100 person-years of serious infections was 5.5 (vedolizumab) and 7.0 (other biologic), with an adjusted hazard ratio of 0.89 (P = .38).
  • In patients with CD, corresponding findings were 7.9 (vedolizumab) and 6.5 (other biologic) with adjusted hazard ratio of 1.15 (P = .16).
  • Rates of clinical response and clinical remission were similar in patients treated with vedolizumab compared with other biologics for both UC and CD.
Time to treatment failure in (A) biologic-naïve. Treatment failure included discontinuation of biologic treatment, IBD nonsurgical hospitalization, primary IBD surgery, and corticosteroid initiation.
Time to treatment failure in (B) biologic-experienced CD patients. 

My take: This large prospective study showed no new safety signals with mean followup of more than 3 years. There were no new trends or changes of clinical importance for infections (serious and opportunistic infections, gastrointestinal infections, respiratory tract infections, other infections), malignancies, infusion-related reactions, hepatotoxicity, and pregnancies. No cases of PML were reported. Efficacy was similar between vedolizumab and other biologics.

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How Does Remission in Crohn’s Disease Affect the Abnormal Microbiome/Gut Signature?

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T Braun et al. Gastroenterol 2026; 170: 971-984. Open Access! Perturbations of Diet and Gut Signatures Persist During Remission in Crohn’s Disease Despite Effective Immune Suppression

Methods: The authors analyzed diet, ileal transcriptomics, microbiomics, and metabolomics across patients with CD in remission, patients with active CD, and non–inflammatory bowel disease (IBD) controls as the reference for healthy signals.

Key findings:

  • Immune signals: Ileal transcriptomics revealed a significant decrease in genes and pathways associated with adaptive T cells and innate granulocytes during remission, which was even deeper than observed in non-IBD controls.
  • Antimicrobial gene expression: Patients in remission showed an increase in the expression of epithelial antimicrobial pathways and related genes, including DUOX2, along with an increase in genes associated with goblet cells and mucin glycosylation.
  • Microbiome and diet: In patients in remission, there was persistent pathogenic gut microbial composition, metabolic alterations, and less healthy dietary habits, which were characterized by a higher intake of ultraprocessed foods and lower consumption of fiber, folate, vitamin C, and vegetables
Purple = control (n=64), Yellow = CD remission (n=56), Red = CD active disease (n=24). Fecal signals persist during remission and substantially correlate with dietary exposures. (A) Boxplots of Faith’s phylogenetic alpha diversity, our previously defined health index,23 the previously defined Gevers IBD dysbiosis index21, and our IBD-specific index23 between controls, CD patients in remission, and CD with active disease.

Fecal signals persist during remission and substantially correlate with dietary exposures. (A) Boxplots of Faith’s phylogenetic alpha diversity, our previously defined health index,23 the previously defined Gevers IBD dysbiosis index21, and our IBD-specific index23 between controls, CD patients in remission, and CD with active disease.

My take (borrowed from the authors): This study shows that, during remission with advanced therapies, “disturbances in antibacterial epithelial signals, along with unhealthy dietary patterns, altered microbiome, and perturbed metabolome, continue and are partly linked to the risk of flare 6 months later.”

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NSAIDs and IBD Flares (2026)

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AS Mayer,et al. Arthritis Care Res. https://doi.org/10.1002/acr.80067. Open Access! Safety of Prescription Nonsteroidal Anti-inflammatory Drugs in Adults With Inflammatory Bowel Disease: Data From a Large Administrative Claims Cohort.

Methods:

  • “This retrospective cohort study included patients with IBD aged at least 18 years from Optum’s deidentified Clinformatics Data Mart Database (2000–2022). Patients with a new NSAID prescription fill were matched to those without an NSAID fill during the study period…Propensity score-based inverse probability of treatment-weighted Cox proportional hazards models evaluated the association between NSAID exposure and time to IBD-related hospitalization across IBD subtypes.”

Key findings:

Unweighted Kaplan-Meier curve for IBD-related hospitalization in patients
with Crohn disease (B).
Unweighted Kaplan-Meier curve for IBD-related hospitalization in patients
with ulcerative colitis (C).

Discussion:

  • “The use of IPTW [inverse probability of treatment weighting] to balance an extensive number of confounders associated with NSAID use optimizes the assessment of the association of NSAID exposure with IBD-related hospitalization and helps address recent concern of residual confounding in observational studies of NSAID risk in IBD.”
  • Besides the potential risk of an IBD flare, “NSAID use is associated with risk of hospitalization from several non-IBD–related entities such as acute kidney injury and adverse cardiac events…a large prospective multicenter observational study of more than 18,000 admitted patients in England found that NSAIDs were responsible for 29.6% of admissions related to adverse drug reactions, including gastrointestinal bleeding, stroke, and renal impairment.34“

My take: This study shows an association of increased hospitalization in patients with CD but not UC based on NSAID exposure. The absolute risk of this appears low and could be in fact related to residual confounders (despite use of IPTW) as this was not a prospective study. The risk of NSAIDs outside the GI tract are likely more significant for most patients. Nevertheless, there are limited options for pain management and NSAID benefits have to be weighed against other approaches.

Related blog post: Rethinking the Link between NSAIDs and IBD Flares

Health Risks from Too Much Dietary Protein

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Sophie Egan, NY Times 5/28/26: 5 Health Risks From Consuming Too Much Protein

An excerpt:

“Most Americans eat more protein than they need. We asked experts what can happen if people have too much of a good thing…

If you’ve browsed the packaged-food aisle of a grocery store lately, or scanned the updated Dietary Guidelines for Americans, you might think that when it comes to protein, more is better…the new inverted food pyramid, released by the Trump administration in January, features protein prominently, with steak, chicken and cheese at the top…

Potential problems can arise when people eat much more than around 1.2 grams of protein per kilogram of body weight per day…

Heart Disease and Type 2 Diabetes

Research suggests that those who eat larger amounts of red and processed meat tend to have higher risks of heart disease and Type 2 diabetes…In one large analysis published in 2023, for instance, researchers found that eating an extra 100 grams of red meat (equivalent to about one thin, boneless pork chop) per day increased the risk of heart disease by 11 percent — and every additional 50 grams of processed red meat (equivalent to about one standard hot dog) per day increased it by 26 percent. Another study, also published in 2023, found that among the nearly 217,000 (mostly female) participants, those who ate the most red meat had a 40 percent higher risk of developing Type 2 diabetes than those who ate the least, and that those who ate the most processed red meat had a 51 percent higher risk…

Cancer

In one study published in 2024, researchers found that diets high in red meat were linked with a 30 percent increased risk of developing colorectal cancer, and that those high in processed meat were linked with a 40 percent increase in risk…People who prioritize vegetables, fruits and whole grains, along with lean or plant-based proteins, are less likely to develop certain types of cancer (as well as cardiovascular disease and Type 2 diabetes).

Constipation and Other Digestive Concerns

People who are focused on increasing their protein consumption (especially those on low-carb diets) sometimes inadvertently leave out high-fiber foods, like vegetables and whole grains [which may increase the likelihood of constipation and irritable bowel syndrome]…

Weight Gain

Excess calories, including those from protein, will be turned into fat…A half-cup of cooked vegetables, for instance, has an average of about 25 calories, whereas a half-cup of cooked chicken has about 140 calories…

Kidney Issues

If your kidneys are healthy, you probably don’t need to worry much about excess protein consumption…for the more than 1 in 7 Americans with chronic kidney disease — especially those who may be close to needing dialysis — metabolizing large amounts of protein can stress the kidneys…Kidney stones are also a potential side effect of consuming too much animal protein.”

My take: The famous line by Mae West “Too much of a good thing can be wonderful!” is not true for dietary protein.

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Geese on the Chattahoochee near Island Ford

Invisible Workload of Caring for Pediatric Patients with Inflammatory Bowel Disease

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Background: “Historically, telephone calls were the primary means of communication between families and clinicians. With the widespread adoption of electronic health records (EHRs) and patient portals, asynchronous digital messaging has become increasingly common. Although these platforms may enhance access and patient engagement, evidence suggests they do not simply replace telephone encounters; instead, they may increase overall communication volume.7 Lower thresholds for initiating messages, the need for iterative clarification, and miscommunication may all contribute to this rise, raising concerns about added workload and potential clinician burnout…Understanding the timing, magnitude, and predictors of between-visit communication is essential to improving care delivery and accurately estimating workforce needs to effectively manage pediatric IBD patients.”

Methods:  From the shared electronic health record, the data from 226 patients (0 to22 years) was quantified. This included outpatient visits, emergency care, and procedures, as well as between-visit care (portal messages from patients, telephone encounters, and clinician-patient review of results) from prediagnosis through long-term follow-up.

Key findings:

  • Between-visit care rose from a median of 1 event per 6 months at time >1 year prediagnosis to 64 events in the year following diagnosis
  • After the first year following diagnosis, between-visit care was a median of 41 events per year
  • There was a strong, graded relationship between disease severity and health care utilization, with the greatest increases seen in subspecialty visits, emergency care, and between-visit care among patients with moderate to severe symptoms
The number of results review and portal message encounters relative to the time of diagnosis
This chart shows the number of telephone encounters relative to the time of diagnosis
Disease severity affects frequency of messages/phone calls.
But, these interactions are frequent even in asymptomatic patients.

Discussion Points:

  • “Even during periods of relative disease quiescence, patients generated substantial volumes of portal messages, telephone encounters, and result review requirements. These findings underscore that the longitudinal management of pediatric IBD extends far beyond scheduled clinic visits and episodic care.”
  • “This persistent care burden likely reflects the complexity of pediatric IBD management including medication titration, symptom monitoring, laboratory surveillance, comorbidity screening, insurance navigation, school-related concerns, anticipatory guidance, administrative needs, transitional readiness planning, and caregiver and patient education.11 Unlike acute care utilization, which may diminish as disease control improves, the need for ongoing communication and care appears intrinsic to chronic disease management in the pediatric IBD population.”
  • “Despite its clinical importance, between-visit care remains largely invisible in traditional utilization metrics and is frequently unreimbursed. Our findings indicate that this hidden workload is substantial, persistent, and closely tied to disease complexity rather than patient demographic factors.”

The editorial from Kellermeyer notes that this invisible care did not include “the substantial administrative workload associated with prior authorization (PA) for advanced IBD therapeutics, insurance denial management, appeals, and peer-to-peer reviews …[which] are notoriously difficult to capture in electronic health record (her) metadata.”

My take: There is a lot of behind the scenes physician work that is needed to help manage patients with inflammatory bowel disease. I suspect most families do not realize the extent of this work.

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