Mechanical Dilation vs. Medical Therapy for Pediatric Eosinophilic Esophagitis

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D Burnett et al. JPGN Reports. 2025;6:19–26. A Canadian multicenter pediatric eosinophilic esophagitis cohort: Evidence for a nondilation approach to esophageal narrowing

This was a retrospective study from Vancouver with 332 new diagnosis of eosinophilic esophagitis (EoE).

Key findings:

  • The incidence of EoE in patients less than 15 years old was 5.4 per 100,000 person‐years
  • Of the 332 new diagnoses, 40 (12.0%) had endoscopically-identified esophageal narrowing at diagnosis
  • During follow-up of 1-4 years, 11 (27.5% of narrowed cohort) patients underwent mechanical esophageal dilation
  • “Our most surprising result was the high number of cases of esophageal narrowing that resolved on follow‐up scope after initiating medical/dietary therapy, without need for mechanical dilation.” The rates of resolution were 1 with 1 (100%) on systemic steroids, 7 out of 13 (54%) with topical steroids, 3 out of 4 (75%) with dietary therapy, and 4 out of 12 (33%) with PPI therapy

My take: This study was a little confusing in how the results are presented. Through most of the article, there are 40 (of 332) children with newly-diagnosed EoE who had narrowing identified. However, there is also discussion of a 65 children subset who had follow-up endoscopy and this is the group in which esophageal narrowing treatment response is reported.

Despite the confusion, the clear take-home message is that esophageal narrowing often responds to medical treatment; only a subset of children with esophageal strictures need mechanical dilatation.

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Over 60% of Initial Nonresponders Improve with Extended Risankizumab Therapy for Crohn’s Disease

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R Panaccione et al. Clinical Gastroenterology and Hepatology 2025; In press. Open Access! Extended Risankizumab Treatment in Patients With Crohn’s Disease Who Did Not Achieve Clinical Response to Induction Treatment

Addendum -updated reference: R Panaccione et al. Clinical Gastroenterology and Hepatology 2025; 23: 2012-2022. Open Access! Extended Risankizumab Treatment in Patients With Crohn’s Disease Who Did Not Achieve Clinical Response to Induction Treatment

Methods: Per the study design, patients who did not achieve SF/APS clinical response following induction could receive 12 weeks of extended treatment with RZB, either via administration of the higher (1200 mg) IV RZB dose evaluated in ADVANCE and MOTIVATE or by initiation of SC RZB at doses (180 mg and 360 mg) used in FORTIFY maintenance therapy.

Key findings:

  • Over 60% of initial nonresponders achieved clinical response with extended RZB treatment. These patients also demonstrated improved clinical and endoscopic outcomes during the extended treatment period, which were sustained or continued to improve during maintenance.

My take: While there is a very good response with initial risankizumab therapy in Crohn’s disease, it looks like judgment on response needs to wait until 24 weeks as there are many who do not respond at 12 weeks who will subsequently respond to treatment.

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Do Setons Improve Outcomes in Anti-TNF Treatment for Fistulas?

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J McCurdy et al. AP&T 2025; https://doi.org/10.1111/apt.70081. The Impact of Setons on Perianal Fistula Outcomes in Patients With Crohn’s Disease Treated With Anti-TNF Therapy: A Multicentre Study

This study included 221 patients — 81 with setons and 140 without setons. Patients were treated with their first anti-TNF therapy for perianal fistulizing Crohn’s disease (PFCD) after undergoing a pelvic MRI between 2005 and 2022 from 6 North American centers. Our primary outcome was major adverse fistula outcome (MAFO), a composite of repeat local surgical intervention, hospitalization, or fecal diversion for PFCD.

Key findings:

  • Patients with setons had similar rates of MAFO (HR 1.23; 95% CI, 0.68–2.21) and fistula remission at 6 months (OR, 0.81; 95% CI, 0.41–1.59) and 12 months (OR, 0.63; 95% CI, 0.31–1.27) compared to patients without setons
  • In patients with abscesses, there were lower rates of MAFO (HR, 0.49; 95% CI, 0.19–1.25) but not statistically significant in patients with setons

My take: This study indicates that seton placement may not be needed in patients who are starting anti-TNF therapy with fistulizing disease, especially if there is not an abscess present.

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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.

“Optimal dietary patterns for healthy aging”

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Tessier, AJ., Wang, F., Korat, A.A. et al.  Nat Med (2025). https://doi.org/10.1038/s41591-025-03570-5. Open Access! Optimal dietary patterns for healthy aging

Key Points:

  • Of >105,000 participants with 30-year follow-up, only 9.3% achieved healthy aging (age 70, w/o any chronic diseases). Their diet was significantly associated with this outcome
  • A Mediterranean type diet high in fruits, vegetables, legumes, nuts, whole grains, low fat dairy products, plant-based foods, and a diet with reduced sodium, trans fats, animal-based foods, sugary beverages, ultra- processed foods was the optimal pattern
These are the specific foods that were linked with healthy aging and other outcomes.
Green-favorable; Red-unfavorable

Eric Topol has provided an excellent commentary on this article for those interested in a deeper analysis: Our Diet and Healthy Aging

Dr. Topol notes that there has been a decline in interest in plant-based foods. “In The Atlantic magazine this week [among other big Signal things ;-)] there was an article (←gift link) on the loss of appeal of plant-based eating…” He also previews his new book Super Agers.

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Essential Learning Objectives in Pediatric Gastroenterology (and All Subspecialties) for Pediatricians and in Pediatric Residency Training

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T Aye et al. J Pediatr 2025; 277, 114380. (Open Access!) Subspecialty Perspectives on the Education Needs for Pediatrics Residency Training

Background: The Council of Pediatric Subspecialties (CoPS) created a list of 3 to 5 learning objectives that each subspecialty believes are the most important practical skills for the general pediatrician and recommends be included in general pediatrics, medicine-pediatrics, and other combined residency program curricula… The Subspecialty Perspectives on (pediatrics) Training (SPoT) action team within CoPS asked each subspecialty representative, most of whom were fellowship program directors at the time, in collaboration with their subspecialty colleagues, to provide a list of 3 to 5 practical learning objectives that should be expected of graduating pediatric residents and practicing general pediatricians in the evaluation and management of conditions related to their subspecialty.

Recommendations for Pediatric Gastroenterology:

My take: This article identifies four of the most important areas in pediatric gastroenterology. If I were to add a fifth, given the wide variety of problems in our field, it would be to know how to quickly reach out to a pediatric gastroenterologist when you need advice.

This article is worth a quick look to see if you have the essential knowledge in all pediatric subspecialty fields (Table 1). One of the most important that relates to pediatric gastroenterology is in the allergy section: “Identify the importance of avoiding indiscriminate testing for food allergy without an appropriate clinical history concerning for IgE mediated food allergy.”

Key Insights on MASLD from Dr. Marialena Mouzaki

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Dr. Marialena Mouzaki recently gave an excellent ground rounds at Children’s Healthcare of Atlanta. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides (with permission).

Key points:

  • Epidemiology: Metabolic associated steatotic liver disease (MASLD) is very common and increasing in prevalence
  • There is new terminology and new diagnostic thresholds
  • Treatment cornerstone relies on lifestyle changes including diet modifications and exercise. Small weight reductions (10 lbs in adults)/improvement in BMI (z reduction of >0.25) can be beneficial
  • Diet: No specific diet has proven more effective than others (eg. low carb, Mediterranean). Avoiding simple sugars is helpful
  • Exercise: US children do not get enough physical activity (goal 1 hour daily). Exercise has not been studied well for pediatric MASLD but it has been proven to reduce cardiovascular disease and premature death
  • Medications: Medications are not part of routine care for pediatric MASLD in 2025 When they are available, use without lifestyle changes could be detrimental (eg. sarcopenia, worse cardiometabolic profile, nutritional deficiencies)
  • Multiple GLP-1 RA-containing agents appear promising (Semaglutide, tirzepatide, survodutide). Resmetirom is FDA approved for the treatment of MASLD with stage 2-3 fibrosis in adults.
  • Treat comorbidities like diabetes, obstructive sleep apnea (OSA), dyslipidemia and hypertension. Treatment of OSA may help MASLD
  • The leading cause of mortality in adults with MASLD is due to cardiovascular disease

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Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults

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JH Hwang et al. JAMA Health Forum. 2025;6(3):e245586. Open Access! Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults

Methods: The authors modeled the effects of four medications,  tirzepatide and semaglutide compared to phentermine-topiramate and naltrexone-bupropion. The study used data from the 2017-2020 National Health and Nutrition Examination Survey. This included 4823 individuals (representing 126 million eligible US adults) aged 20 to 79 years who would meet the following clinical trial inclusion criteria for these drugs: (1) had a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or greater or (2) had a BMI between 27 and 29.9 and at least 1 weight-related comorbidity (ie, diabetes, hypertension, dyslipidemia, or cardiovascular disease).

Key results:

  • Based on this model, in US adults, over a lifetime, tirzepatide would avert 45,609 obesity cases per 100,000 individuals and and semaglutide would avert 32,087 cases per 100,000 individuals.
  • Tirzepatide and Semaglutide would avert cases of diabetes by 20,854 per 100,000 individuals and 19,211 cases per 100,000 individuals respectively.
  • Tirzepatide and Semaglutide would avert cardiovascular disease cases by 10,655 per 100,000 individuals and 8,263 cases per 100,000 individuals respectively.
  • Despite the largest incremental QALY gains of 0.35 for tirzepatide and 0.25 for semaglutide among all antiobesity medications, the incremental cost-effectiveness ratios were $197,023/QALY and 467,676/QALY, respectively.
  • To reach the $100,000/QALY threshold, their prices would require additional discounts by 30.5% for tirzepatide and 81.9% for semaglutide from their current net prices.

In short, the authors indicate that based on a typical QALY threshold for cost-effectiveness, tirzepatide would need to be priced at $4,334 per year, from the current average of $6,236 per year; semaglutide would need to be $1,522 per year, from an average of about $8,412 per year today.

My take: The costs of these drugs in non-US markets would meet the QALY threshold for cost-effectiveness. However, until the patent on these drugs expires, US consumers are likely to be spending a great deal more. The U.S. patent on semaglutide will expire in 2032, and the U.S. patent on tirzepatide will expire in 2036.

CNN 9/24/24 ‘Greed, greed, greed’: Sanders demands Ozempic maker lower prices: “He {Bernie Sanders] noted that the list price for a four-week supply of Ozempic is $969 in America, but the drug can be purchased for $155 in Canada, $122 in Denmark and $59 in Germany. Similarly, Wegovy’s list price is $1,349 in the US, but it costs $186 in Denmark, $140 in Germany and $92 in the United Kingdom.”

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Tirzepatide: Breakthrough in Obesity and Diabetes Management (SURMOUNT-1 Study at 3 years)

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AM Jastrebofff et al. NEJM 2025; 392: 958-971. Tirzepatide for Obesity Treatment and Diabetes Prevention

Methods: In this phase 3, double-blind, randomized, controlled trial, there were  2539 participants with obesity, of whom 1032 also had prediabetes. They were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo.

Key findings:

  • Weight loss: At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was −12.3% with the 5-mg dose, −18.7% with the 10-mg dose, and −19.7% with the 15-mg dose, as compared with −1.3% among those who received placebo (P<0.001 for all comparisons with placebo).
  • Type 2 Diabetes Reduction: Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12)

My take: This study shows durable effectiveness of tirzepatide over a three year period with no new safety signals.

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Exploring Walgreens’ Collapse: The Role of PBMs

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This newsletter explains why Walgreens is collapsing. My concern is that even a company as big as Walgreens had hardly any control over the declining reimbursements for their pharmaceutical sales. They had to accept the reimbursement due to a lack of leverage related to the consolidation of insurance companies and pharmacy benefit managers (PBMs). Without intervention to reverse the ongoing consolidation of these companies (as well as hospitals), patients will face fewer choices and higher costs. Physician groups will face existential business threats.

Here’s an excerpt from the newsletter:

Walgreens is America’s second-largest drug store chain, and has been a public company for more than 100 years… it has closed a thousand stores since 2018, and plans to shut 1,200 more this year…

The real reason Walgreens, and the pharmacy business in general, is dying, is because of a failure to enforce antitrust laws against unfair business methods and illegal mergers…Moreover, even today, the other financial numbers from Walgreens aren’t bad. Sales aren’t going gangbusters, but the number is basically increasing, and so are the number of 30-day prescriptions, even though they’ve cut the number of stores every year since 2017…

But in its main line of business – pharmaceuticals – Walgreens doesn’t set prices. Insurance companies do. And there’s the rub…Walgreens gets a set reimbursement from that consumer’s insurance company for that medication. How much does it get? Well, those insurance company’s contract with what’s called pharmacy benefit managers (PBMs) to manage negotiations with pharmacies…

Theoretically, both sides have some leverage in this negotiation. If a pharmacy chooses not to accept the prices and terms offered by those PBMs, then consumers who have an insurance company that uses that PBM just won’t go there…Pricing wasn’t a big problem for Walgreens when there were lots of PBMs, because it had the ability to say no if the deal was unreasonable, and still maintain a flow of customers…Today, there are really only three PBMs – Express Scripts, Caremark and OptumRx – serving 80% of customers…

In 2015, the big three, with their market power, began lowering reimbursement rates on pharmacies and charging a host of new fees…

PBMs, however, are engaged in a sort of industry-specific arson. And we can see this dynamic by looking at independent pharmacies writ large, nearly one in three of whom have closed in the last ten years. Today, 46% of U.S. counties now have pharmacy deserts, meaning no pharmacies at all…

326 pharmacies have closed since December of 2024. Why is that month significant? Well, that’s the month Elon Musk tanked legislation to address some of the monopolistic squeezing that PBMs are putting on pharmacies and consumers.

Related explanation of PBMs (Dr.Glaucomflecken): The Middlemen of Healthcare (includes useful organizational flowchart)

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Competition for Competitive Acid Blockers

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Thanks to Ben Gold for the reference in today’s post.

J-H Oh et al. Am J Gastroenterol 2025; DOI: 10.14309/ajg.0000000000002929 Randomized, Double-Blind, Active-Controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan Compared With Esomeprazole in Erosive Esophagitis

Introduction: “Unlike PPIs, metabolism of zastaprazan in not dependent on CYP2C19, and it does not require enteric coating due to its acid stability. While PPIs bind irreversibly only to active proton pumps, zastaprazan can bind reversibly and competitively to both active and inactive proton pumps. Moreover, as prodrugs, PPIs necessitate activation into their active form within acidic conditions, typically requiring a regimen of 3-5 consecutive days of dosing…By contrast, P-CABs deliver a rapid onset of action and complete efficacy from the initial dose, as they can directly inhibit proton pumps.”

Methods: A phase III, multicenter, randomized, double-blind, noninferiority clinical study was conducted with 300 subjects (>19 yrs) with confirmed erosive esophagitis compared daily zastaprazan (20 mg) to esomeprazole (40 mg)

Key findings:

  • The cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) (P = 0.178) for esomeprazole.
  • The healing rate at week 4 in the zastaprazan group was higher than the esomeprazole group (95.14% [137/144] vs 87.68% [121/138]; P = 0.026)

My take: Zastaprazan had higher healing rates at 4 weeks; results at 8 weeks were similar. This phase 3 study suggests that there will be other CABs besides vonoprazan approved for treating acid-related disorders.

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