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Big Studies Supporting Combination Advanced Therapy for Ulcerative Colitis and Crohn’s Disease

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An excerpt:

Two [randomized controlled] Phase 2b trials enrolled patients with moderate-to-severe disease who had already failed one or more therapeutic classes of drugs…

One trial analyzed 693 patients with Crohn’s disease, while the other analyzed 572 patients with ulcerative colitis…The trials tested an experimental therapy that combined golimumab and guselkumab, which are already in the market…

In the Crohn’s trial, 49.2% of the most treatment-resistant patients who received a high dose of the combination therapy achieved clinical remission after 48 weeks, compared to 27.3% receiving guselkumab and 23.1% taking golimumab…And the safety profile was about the same. The results of the ulcerative colitis trial showed a similar pattern.

DUET-CD study
“In the overall population, JNJ-4804a demonstrated higher clinical remissionb rates (50.8%) and endoscopic responsec rates (38.1%) versus golimumab (25.4% for clinical remission, 19.8% for endoscopic response) at Week 48. The JNJ-4804 rates were also numerically higher than the rates achieved with guselkumab (42.5% for clinical remission and 33.9% for endoscopic response).”

DUET-UC study
“In the overall population, JNJ-4804a demonstrated superior clinical remissiond rates compared to golimumab, with 41.0% of JNJ-4804-treated patients achieving clinical remission at Week 48 versus golimumab (11.5%), and numerically higher rates than guselkumab (34.0%).”

“Based on results from the Phase 2b DUET studies, Johnson & Johnson will be initiating the Phase 3 DUET ENCORE-CD trial in adults with moderately to severely active CD as well as the Phase 3 DUET ENCORE-UC trial in adults with moderately to severely active UC.”

My take: In both of these phase 2b trials, the combination therapy was more effective than either guselkumab or golimumab monotherapy. The combination therapy was about 8% and 7% more effective for Crohn’s disease and Ulcerative colitis, respectively, compared to guselkumab monotherapy in terms of clinical remission.

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Sunset at Kiawah Island, SC

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.

    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 motorcycle, 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

    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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    Proactive Therapeutic Drug Monitoring is Routine Part of Pediatric IBD Care Plus SNL Humor

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    RJ Colman et al. Crohn’s & Colitis 360, Volume 7, Issue 3, July 2025, otaf050. https://doi.org/10.1093/crocol/otaf050. Open Access! Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease: A Nationwide Survey of Anti-TNF Therapy Practices, Attitudes, and Barriers 

    Methods: A 28-item survey of therapeutic drug monitoring (TDM) was deployed through the ImproveCareNow Learning Health System Network between February and June 2023.

    Key findings:

    • Among 380 invitees, 256 (77%) completed the questionnaire. Among respondents, 67% (171) were academic-affiliates
    • In contrast to the adult literature, most pediatric gastroenterologists report undertaking proactive TDM for anti-TNF agents in IBD management
    • TDM: All 256 respondents reported using TDM for infliximab, while 252 (98%) used TDM for adalimumab (ADL)
    • Proactive TDM: Proactive TDM was more common for infliximab 98% (205/256) compared to ADL 92% (232/252; P = .0007)
    • Overall, 61% (156/255) of respondents reported that they experienced barriers in undertaking TDM. Insurance denial (50%) and cost (31%) were the 2 most commonly reported barriers
    Frequency of therapeutic drug monitoring use stratified by anti-TNF agent.

    Limitation: Only surveyed practitioners in ICN. However, “approximately 65% of US pediatric gastroenterologists practice within ICN-affiliated institutions, [thus] our findings likely reflect national trends.”

    My take (borrowed from authors): “Proactive TDM, is a widely practiced strategy, and represents the current standard of care among pediatric gastroenterologists in the United States.” 

    How to explain a complication with Will Ferrell, YouTube Link: SNL Post-Op (5 minutes)

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    Management of Colorectal Adenomas in Adolescents

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    BJ Hoskins et al.  J Gastroenterol Hepatol. 2026 Apr 24. Open Access! Incidental Colorectal Adenomas in Adolescents: Clinical Management, Genetic Evaluation, and Surveillance (Review article)

    Key points:

    • “Although most isolated colorectal adenomas identified in adolescents are ultimately sporadic, their rarity at this age justifies a lower threshold for genetic evaluation—without routine shortening of surveillance intervals in the absence of hereditary disease”
    • “Current guidelines recommend initiating upper gastrointestinal surveillance at age 20–25 years for FAP and attenuated FAP [17]. Notably, a meta-analysis reported that 42% of children with FAP who underwent EGD had duodenal adenomas…, supporting the biological rationale for upper gastrointestinal screening once a polyposis syndrome is identified”
    • Table 1 lists polyposis syndromes that can be associated with isolated adenomas in adolescents
    • “All visible adenomas should be completely removed when technically feasible'”

    My take: This review provides useful guidance when identifying an adenomatous polyp in the pediatric age group.

    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

    How Helpful is FLIP for Pyloric Dysfunction?

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    A Porto et al. JPGN Reports. 2026;7:59–63. Open Access! Feasibility and clinical value of pyloric functional luminal imaging probe in an infant

    Case report: “This case highlights the feasibility, safety, and clinical effectiveness of FLIP as a diagnostic and treatment tool in an infant with pyloric dysfunction.”

    In brief, the authors describe a former 26 week premature infant with gastric dysfunction with gastric output >100 mL/kg/day while on GJ feeds. “His history was notable for necrotizing enterocolitis with multiple intestinal perforations and bowel resections with resultant short bowel syndrome (97 cm small bowel, intact colon) and chronic respiratory failure requiring tracheostomy and mechanical ventilation.” After obtaining FLIP measurements, IPBI (intrapyloric botulinum toxin injection) was performed with 100 international units of botulinum toxin A. Esoflip dilatation was performed using a 20 mm balloon. This led to full tolerance of gastric bolus feeds. When symptoms recurred, repeat IPBI and dilatation were performed with resolution of symptoms.

     FLIP demonstrated high pyloric pressures up to 105 mmHg,
    Max diameter 13.3 mm (arrow) at 45 mL balloon inflation 

    My take: I am not an expert on FLIP; however, it does not appear to be needed in this situation. Many practitioners would recommend botox injection with or without dilatation in patients with this type of presentation without using FLIP. The authors acknowledge that there are a “lack of reference values for infants” which makes FLIP interpretation more subjective.

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    Beneficial GI Effect of GLP-1 Receptor Agonists: Lower Risk of Peptic Ulcer Disease

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    P Seika et al. Clin Gastroenterol Hepatol 2026; 24: 974-985. Glucagon-like Peptide-1 Receptor Agonists Are Associated With a Lower Risk of Peptic Ulcer Disease: A Nationwide Cohort Study

    Background: “Emerging evidence suggests that GLP-1RAs may exhibit anti-inflammatory properties and could play a role in GI mucosal protection. Proposed mechanisms include the suppression of proinflammatory cytokines, attenuation of reactive oxygen species, and enhancement of mucosal defences, which may reduce susceptibility to PUD.”

    Methods: This was a nationwide retrospective study of adults with T2DM (66,102 participants) using the “All of Us” National Institutes of Health database, including a sub-group analysis of adults who were newly initiated on GLP-1RAs or insulin as second-line therapy. 

    Key findings:

    • After adjusting for possible confounders, GLP-1RAs were associated with significantly lower odds of PUD diagnosis (adjusted odds ratio 0.56; P < .001)
    • Our subgroup included a total of 3313 patients (1270 new GLP-1RA users; 2043 new insulin users). In this analysis, switching to a GLP-1RA as second-line therapy was associated with a significantly lower hazard of PUD compared with switching to insulin (adjusted hazard ratio [HR], 0.44; P < .001)

    My take:

    1. GLP-1 RAs are a remarkable advance. However, we need still more long-term data. Many times in healthcare, new treatments often receive a lot of favorable studies/good press. Over time and with more scrutiny, more adverse effects become evident.
    2. Though these medications can cause a lot GI symptoms, it is helpful to know that they are associated with a lower risk of peptic ulcer disease.

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