How Does Prior Topical Steroids Affect Response to Dupilumab for Eosinophilic Esophagitis

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M Chehade et al. Am J Gastroenterol 2026; 121: 649-660. Open Access! Dupilumab Efficacy in Children With Eosinophilic Esophagitis With Prior Swallowed Topical Corticosteroid Use: A Subgroup Analysis Thanks to Ben Gold for this reference.

Background: “The aim of this exploratory, post hoc subgroup analysis of EoE KIDS was to assess dupilumab efficacy and safety in patients aged 1–11 years with EoE previously treated with STCs” [swallowed topical corticosteroids]. This study further examined th EoE KIDS cohort (Chehade M, Dellon ES, Spergel JM, et al. Dupilumab for eosinophilic esophagitis in patients 1 to 11 years of age. N Engl J Med 2024;390(24):2239–51.)

Methods: The trial consisted of the following: part A, a 16-week, randomized, double-blind, placebo-controlled treatment period; part B, a 36-week, extended active treatment period in which patients knew that they received active treatment but did not know their regimen; and part C, a 108-week, open-label extension period in which all patients received higher-exposure dupilumab. Eligible patients were aged 1–11 years with a confirmed diagnosis of active EoE who were unresponsive to ≥8 weeks of PPIs.

Of 102 patients, 82 (80%) received prior STCs and 59 (58%) had prior inadequate response, intolerance, and/or contraindication (IRIC) to STCs.

Key findings:

  • At W16, higher-exposure dupilumab improved rates of histologic remission vs placebo in patients with prior STC use (60.7% vs 0.0%) and prior IRIC to STCs (60.9% vs 0.0%).
  • Responses were maintained at W52 with higher-exposure dupilumab, with improvements observed in patients who switched from placebo to higher-exposure dupilumab.
  • “Findings seemed comparable in those without prior STC use or prior IRIC, although patient numbers were small.” Only 9 patients in the treatment cohort did not haver prior STC use.

My take: It appears that dupilumab works well in those with and without prior swallowed topical corticosteroids (STCs). Though the numbers are small, the response appears more robust in those without prior STCs; perhaps, those with prior STC failure had more refractory EoE.

Some good brief YouTube EoE educational videos for families from GIKids.org (with pharmaceutical funding), links:

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Appendectomy for Refractory Ulcerative Colitis: 2026 COSTA Study

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Visser E, Reijntjes M, Heuthorst L et al.The Lancet Gastroenterology & Hepatology, 2026; 11, 190-203. Appendicectomy versus switching to a JAK inhibitor in inducing remission in patients with active ulcerative colitis after biologic therapy failure (COSTA): 1-year results of a multicentre, prospective, cohort study

Last year, the ACCURE Trial (see blog post link below), showed that laparoscopic appendicectomy, in addition to standard medical therapy, significantly reduced the relapse rates for ulcerative colitis (UC) within 1 year. Most patients were treated with mesalamine.

The COSTA study examined adult patients (n=125) who were not responding to advanced therapy. Patients were offered one of three treatments: laparoscopic appendicectomy while continuing their existing advanced therapy at a stable dose; switching their advanced therapy to a JAK inhibitor; or colectomy. 116 patients were included in the modified intention-to-treat-analysis (67 received appendicectomy and 49 received JAK inhibitor (primarily tofacitinib).

Key findings:

  • 22 (32.8%) of 67 patients in the appendicectomy group were in clinical remission without therapy failure at 12 months compared with six (12.2%) of 49 patients in the JAK inhibitor group (p=0.016)
  • At 12 months, corticosteroid-free clinical remission without therapy failure was attained in 22 (32.8%) of 67 patients in the appendicectomy group compared with six (12.2%) of 49 patients in the JAK inhibitor group  (p=0.010). Clinical response in 49 (73.1%) of 67 patients compared with 26 (53.1%) of 49 patients (p=0·025), and endoscopic response in 31 (48.4%) of 64 patients compared with 11 (25.6%) of 43 patients (p=0·018)

My take (borrowed in part from the authors): “Appendicectomy as an adjunct to advanced therapy in biologic-exposed patients with active ulcerative colitis was associated with higher clinical remission rates at 12 months compared with switching to a JAK inhibitor.” We don’t know how appendectomy would influence disease course in pediatric patients. We also don’t know how this information will be incorporated into adult guidelines.

Interestingly, there have been studies (two cited below) indicating that appendectomy lowers the risk of developing inflammatory bowel disease:

Related blog post: ACCURE Trial: Appendectomy As an Adjunct Ulcerative Colitis Treatment Plus One

Kiawah Island at Sunrise

    Dr. Stacy Kahn: Clostridioides difficile 2026

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    Recently, Dr. Stacy Kahn gave our group an excellent update on Clostridioides difficile. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides. Dr. Kahn has been a leader on treatment and advocacy for C. difficille. In 2025, she received the Leadership Award from the Peggy Lillis Foundation recognizing her clinical, research and advocacy efforts related to C. difficile awareness and treatments.

    Key points:

    Diagnosis: C. diff is difficult to diagnose. The NAAT-based assays are highly sensitive but cannot readily distinguish active infection from colonization. ELISA toxin assays have higher specificity. However, there are many of these assays and their reliability in identifying active infection from colonization varies. In individuals with underlying diseases like IBD and IBS, this can create uncertainty about the diagnosis of C. diff.

    Presentation: Symptoms are quite variable, from asymptomatic to bloody diarrhea to fulminant colitis (uncommon in kids). Profound urgency is a common feature.

    Transmission: C. diff bacteria can survive on surfaces for 24 hrs. The spores can survive months to years. In addition, the (invisible) spores are highly resistant to heat, disinfection and antimicrobials. Thus, nursing homes and hospitals are frequent reservoirs.

    Epidemiology: C diff rates in the hospital setting have improved, likely due to antibiotic stewardship. Community rates have increased; though, precise estimates are problematic as the diagnostic testing is not straightforward.

    Costs: In 2016, the estimated annual costs due to C diff were $ 6.3 billion (Zhang S. et al. BMC Infect Dis. 2016).

    Resources/Websites:

    Severe C diff in Children: In a retrospective study of C diff in hospitalized children (2013-2019, n=17,142 children) showed that among 23,053 CDI admissions, 74 (0.3%) had a colectomy (55 in IBD patients), and 29 (0.1%) had toxic megacolon. All-cause mortality was noted in 429 (1.9%) (Reference: Edwards PT, Kahn SA, Nicholson, M et al. J Pediatr. 2023; 252:111-116.e1. Open Access! Clostridioides difficile Infection in Hospitalized Pediatric Patients: Comparisons of Epidemiology, Testing, and Treatment from 2013 to 2019).

    Testing: Recommendations include avoiding testing in those taking laxatives; however, an exception to this would be patients with motility disorders. Even combination testing cannot always distinguish between colonization and active infection. In addition, there are numerous toxin tests with variable performance.

    [From prior blog post: In a large adult study with 293 of 1416 hospitalized adults testing positive for C. diff, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method. (Overdiagnosis of Clostridium difficile with PCR Assays)]

    Treatment:

    • 1st line treatment remains vancomycin.
    • 10-day treatment course is recommended.
    • Fidaxomicin, particularly for recurrrent C. diff could be helpful and easier to administer (2/day).
    • Prophylactic treatment (low dose vancomycin) may be appropriate in high risk individuals needing to take antibiotics.
    • FMT is no longer readily available from stool banks. Donor-directed FMT may be an option after appropriate screening. Given the lack of stool banks, urgent treatment with FMT for severe cases is not available.
    • Probiotics have not been proven effective in reducing recurrence and increase the costs for families. A diet high in fruits and veggies (‘eat the rainbow‘) could help restore a more healthy microbiome.
    • Newer treatments in adults, Vowst and Rebyota, are expensive and not readily available for children. Anecdotal reports suggest they may be beneficial in pediatric patients.

    Conclusions: C diff research is difficult in pediatrics. Many of the patients who need treatment would be excluded from trials. There are very few treatment options in kids.

    Related blog posts:

    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.

    Essential Summer Safety Tips for Preventing Drowning

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    I am reposting this from last year with slight modifications.

    An ICU colleague indicated that she really does not like to work on summer holiday weekends. While she is a hard worker, what she doesn’t like is seeing kids with drowning and firework injuries. All of a sudden a happy time becomes tragic. With that in mind, here are a few tips to prevent drowning.

    From Strong4Life: “Practicing water safety for kids of all ages is crucial because drowning is a leading cause of death in children from birth through the teen years. And drowning is often quick and silent.”

    Also, firearm deaths are the leading cause of death in children in the U.S. and motor vehicle accidents are second. So, firearms need to be secured and drive safely on the way to the pool, lake, river or beach.

    Related blog posts:

    C Raymond-King et al. N Engl J Med 2026;394:1958-1959. Open Access!
    Current Causes of Death among Children and Adolescents in the United States

    Legislating Directed-Donated Blood

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    JW Jacobs et al. N Engl J Med 2026;394:1667-1669.
    Legislating Medicine — Directed Donation and the Politics of Patient Choice

    In a previous post )Increase in ‘Unvaccinated’ Blood Requests), the increase in requests for directed-donated blood to avoid “vaccinated” blood was discussed. This article describes pending legislation in Tennessee to make this a patient right.

    An excerpt:

    In February 2026, members of the Tennessee General Assembly introduced House Bill 2166 (HB 2166, “An Act to Amend Tennessee Code Annotated, Title 68, Chapter 32, Relative to Blood Donations”), which would require blood banks and hospitals to comply with directed-donation requests for patients scheduled for medical procedures.1 Its sponsors framed the bill as protecting patient choice by ensuring that patients have the right to select what is put into their bodies. The paradox is that the U.S. community blood supply is already among the safest in the world, the product of decades of evidence-based practice, universal donor screening, and rigorous infectious disease testing. HB 2166 does not fix a broken system. Instead, it risks undermining one that already functions safely and effectively — which is precisely why this legislation merits attention in domains beyond the blood bank. The bill exemplifies a broader pattern in which politicians seek to legislate medical practice in ways that override scientific consensus while invoking the language of autonomy and choice…

    What is emerging is not an expansion of evidence-based patient rights but a distortion of them. The patients’ rights movement of the 1970s — built around informed consent, refusal of treatment, and shared decision making — led to genuinely important protections, but it envisioned those rights operating within the framework of evidence-based medicine, not as mechanisms to compel clinicians to provide interventions that scientific organizations and medical societies have identified as harmful…HB 2166 and related bills do not just expand patient choice; they transform misinformation-driven preferences into enforceable medical policy, granting pseudoscientific fears the force of state law. The result, unfortunately, is not patient empowerment, but legislated harm delivered with the imprimatur of democratic governance.

    This dynamic extends well beyond transfusion medicine. Similar patterns are increasingly visible in vaccine policy, public health governance, and reproductive care. 

    My take: When a person decides to take additional risks (eg. riding a motorcylce, drinking raw milk, not using a seat belt), the consequences primarily impact that individual. However, it does not feel right to compel others to assist in delivering substandard care. Though, HB 2166 does not waive existing donor-eligibility and safety requirements, it could still lead to delays in care with worsened outcomes.

    Victoria Island, Argentina

    HHS Removes Experts from United States Preventive Services Task Force (USPSTF)

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    AMA Statement:

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    “GLP-1 Receptor Agonists and Eating Disorders — Cause for Concern”

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    A Banks. N Engl J Med 2026;394:1665-1667. GLP-1 Receptor Agonists and Eating Disorders — Cause for Concern.

    An excerpt:

    Constraining the growth of the global obesity epidemic would have clear benefits at the individual and population levels. Use of GLP-1 drugs has been linked in some patients to improved cardiovascular outcomes, a reduced risk of kidney disease, a reduced desire to drink alcohol, and potentially protective effects against neurodegenerative diseases. It is therefore easy to understand the substantial interest in investing in the development of these products and the optimism about their public health effects.

    Nonetheless, some worrisome signals have emerged…The proportion of GLP-1 receptor agonist prescriptions that were written for people without diabetes, obesity, or overweight increased from 4.5% in 2018 to 17% in 2023…1

    There is also compelling preliminary evidence suggesting that the use of these drugs could exacerbate and lead to new diagnoses of restrictive eating disorders, including anorexia nervosa…3 Lifetime prevalence of anorexia nervosa is as high as 6.3% in women and 0.3% in men,4 and the risk of death from any cause among people with anorexia nervosa is more than five times as high as that in the general population…5

    Nutrient deficiencies, electrolyte abnormalities, orthostatic hypotension, osteopenia, sarcopenia, thinning hair, and other signs of malnutrition have been observed [in users of GLP-1 agents], and the effects of long-term use are still largely unknown…

    The cumulative incidence of new eating-disorder diagnoses (most commonly anorexia nervosa) in the full study population was 1.275%…3 this proportion translates to more than 420,000 people who could develop a related eating disorder with long-term use.

    Physicians, trialists, regulators, policymakers, and drug developers are unprepared for this coming wave.

    My take: GLP-1 RAs are not for everybody; they will likely contribute to eating disorders in many patients.

    GLP-1 RAs also have been associated with a higher risk of Nonarteritic Anterior Ischemic Optic Neuropathy (aka ‘eye stroke’) in approximately in 1 in 10,000 recipients. One reference: JAMA Ophthalmology. 2026;144;(3):259-264. New-Onset Nonarteritic Anterior Ischemic Optic Neuropathy and Initiators of Semaglutide in US Veterans With Type 2 Diabetes

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    Trail to Mt Fitz Roy (Argentina)

    Beneficial Off-Target Effect: Upadacitinib Improved Eosinophilic Esophagitis (Case Report)

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    N Nguyen , M Bauer. JPGN Rep. 2026;1-3.  Successful treatment of eosinophilic esophagitis with upadacitinib prescribed for atopic dermatitis. doi:10.1002/jpr3.70170

    This case report describes a 15 yo with severe atopic dermatitis and multiple atopic diseases whose eosinophilic esophagitis remained in remission after starting upadacitinib, a JAK1 inhibitor, and stopping dupilumab. JAK1 inhibitors, such as upadacitinib and abrocitinib, are approved for severe AD. 

    The discussion notes that there had been a prior case report of tofacitinib, a JAK1/JAK3 inhibitor, effectively treating refractory EoE. The authors “hypothesize that JAK inhibition of key Th1 and Th2 signaling pathways including IL-4, IL-13, and TSLP could effectively treat EoE, while also treating AD.”

    My take (borrowed from authors): “If upadacitinib is used for the treatment of AD, cessation of other therapies for EoE, particularly biologics like dupilumab, should be strongly considered.”

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    AI Pilot Prescription Renewal in Utah

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    S Gerke et al. NEJM 2026; 394: 1561-1563. Utah’s Prescription-Renewal Pilot Program — Autonomous AI Managing Patient Care

    An excerpt:

    In January 2026, Utah rolled out a 12-month pilot program involving an AI system developed by health tech startup Doctronic that autonomously renews certain prescriptions for people with chronic conditions…1,2

    Although the program is limited to prescription renewals for 192 commonly prescribed drugs (see box),1,2 it could pave the way for expanded initiatives that include additional products, autonomous initial prescribing, and broader geographic areas…

    One question is whether it targets a clinically meaningful problem. The stated purpose is to address medication nonadherence…Automated medication-refill programs for various classes of drugs, including antihypertensives, lipid-lowering agents, and antidiabetic agents, have meaningfully increased adherence…4

    Autonomous renewal would be inappropriate for medications requiring frequent dose adjustments or in patients whose clinical status could change rapidly…physician oversight to detect early signs of toxic effects, disease progression, or changing organ function that would necessitate dose modification…AI-based refill generation without a defined end point may preclude opportunities for physician–patient discussions that could curb polypharmacy or medication overuse.

    The Utah program could also present legal problems. Doctronic’s AI system, which reportedly hasn’t been reviewed by the Food and Drug Administration (FDA),1 should probably be considered a device under the Federal Food, Drug, and Cosmetic Act (FDCA)…

    Another FDCA provision specifies that dispensing a prescription drug constitutes misbranding — a violation carrying potential civil or criminal penalties — unless it occurs “upon a written prescription of a practitioner licensed by law to administer such drug” or upon an oral order that is promptly turned into a written order by the pharmacist…

    It is unclear whether Utah’s AI system complies with these requirements. Even if Utah allows AI-based prescribing in the absence of supervision by a licensed physician or other prescriber, federal law would preempt state law…

    The FDA may decide to look the other way and allow this experiment to continue, leaving clinicians and patients without safety assurances amid an extraordinary expansion of autonomy for AI.

    My take: There may be many situations in which agentic AI would be helpful with pharmacy management. However, until this technology is proven to be safe, like all other devices, it should be limited to situations in which the prescribing physician is in agreement with this process.

    Related blog post:

    Peony (blooms here in late April)

    The Mother of Invention: Central Line Vest to Reduce Complications

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    RE St Pierre-Hetz et al. JPGN Reports. 2026;1–6. A novel central line securement vest reduces line trauma and improves quality of life in patients with intestinal failure

    This single center study compared a novel central line securement vest (n=12) to traditional securing methods (n=11).

    Key findings:

    • The vest group had lower rates of line trauma during the period of vest use versus prior to its use. The rates of infections and replacements were a little lower during vest use (not statistically-significant) compared to prior to use. The control group had similar rates of trauma, infections, and replacements before and during the study period.
    • The vest group had much higher rates of line issues prior to vest use than the control group
    • 5 of the 12 vest patients discontinued use before the planned 12-month evaluation

    The story behind the inventor is fascinating as well. “Gus Gear” was “founded by Sarah Palya over a decade ago after her son Gus was diagnosed with intestinal failure.” Due to this, he required long-term parenteral nutrition. “Gus also has autism, and his constant movement and activity put him at risk for accidental line trauma and infection. Sarah looked for ways to secure his central line while also allowing him to live as normally as possible, without severely restricting his activity. Finding no solutions, she sat down at her sewing machine and created the very first Gus Gear Central Line Vest to secure his catheter.” The company now makes a similar product to secure GTubes, LOCK 3000 Belt.

    My take: This small study supports the use of this product, especially in those prone to line trauma: Gus Gear Central Line Vest® (Dr. Hochman has no commercial ties to this company)

    Origin of the expression: “Necessity is the mother of invention“

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