Category Archives: inflammatory bowel disease

Upadacitinib for Pediatric Ulcerative Colitis

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A Yerushalmy-Feler A et al. Clinical Gastroenterology and Hepatology, 2026 (In press); Upadacitinib Maintenance Therapy in Pediatric Ulcerative Colitis: 52-Week Multicenter Study From the Porto Group of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition

Background/Methods: There is limited data on the use of upadacitinib for pediatric inflammatory bowel disease. This retrospective data from 35 European centers analyzed its effectiveness in 105 children (95 with UC and 10 with IBD-U).  Prior to upadacitinib, 103 of 105 children (98%) were treated with biologic therapies and 79 (75%) with ≥2 biologics. The induction dose was 45 mg in 86% of cohort; the maintenance dose was 30 mg in 87% (only 2 patients received 45 mg maintenance). Mean age at IBD diagnosis was 11.3 yrs and mean age at start of upadacitinib was 14.6 yrs. 65% of study participants had a pancolitis.

Key findings:

  • Clinical remission and corticosteroid-free clinical remission (CFR) were observed after 8 weeks in 61 (58%) and 53 (51%) children, respectively
  • By week 52, 75 children (71%) achieved clinical remission, 73 (70%) achieved CFR, and sustained CFR in 63 (60%); CFR with FC <150 mcg/g was reached 30 of 80 (38%) (29% of the ITT group)
  • Adverse effects: There were two serious AEs: an appendiceal neuroendocrine tumor and cytomegalovirus colitis. The most frequent AEs were hyperlipidemia (n = 20), infections (n = 18), and acne (n = 14)

Predictors of response: “The baseline variables that were associated with achieving sustained CFR were prior failure of fewer biologic agents (≤2 vs >2), a lower PUCAI score, absence of corticosteroid therapy, and higher serum hemoglobin and albumin levels.”

Age: “Our findings suggest that upadacitinib provides comparable effectiveness in younger children weighing <40 kg, supporting its therapeutic potential across a broader pediatric age and weight range.”

My take: Upadacitinib is an important therapy for ulcerative colitis in the pediatric age range and in adults. It is effective in all age groups. Also, young children can now be prescribed a liquid version (Rinvoq LQ) which requires twice daily dosing (rather than once a day). Some patients who do not respond adequately or lose response may benefit from higher dosing.

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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.

Case Report: Car-T for Refractory Ulcerative Colitis

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 F Muller et al. NEJM 2025;393:1239-1241. CD19 CAR T-Cell Therapy in Multidrug-Resistant Ulcerative Colitis

This case study involved the use of “autologous chimeric antigen receptor (CAR) T cells targeting CD19 in a 21-year-old woman with severe multidrug-resistant ulcerative colitis, who had declined colectomy. Previous treatments with prednisolone, mesalamine, infliximab, ustekinumab, ozanimod, filgotinib, vedolizumab, upadacitinib, and cyclosporine combined with mirikizumab had not induced clinical remission.”

“Clinical and biochemical remission occurred and were maintained over the 14-week follow-up period… without the use of concomitant therapy. Endoscopic, histologic, and ultrasonographic assessments showed signs of mucosal healing over time….These data suggest the possibility that CD19 CAR T-cell therapy can induce rapid drug-free remission in refractory ulcerative colitis, a disease that was previously thought to be largely B-cell–independent, given that rituximab treatment showed no efficacy..”

My take: This is only a single case report. However, it shows that modulation of the immune system could potentially cure ulcerative colitis. At the same time, long term adverse effects of CAR-T therapy will need to be monitored.

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Detecting Preclinical Crohn’s Disease in First-Degree Relatives with Biomarker Screening

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D Turner et al. . Gut 2025;0:1–7. doi:10.1136/gutjnl-2025-336368. Preclinical stages of Crohn’s disease defined by faecal calprotectin in asymptomatic first-degree relatives: screening framework for prevention trial

Methods: “Faecal calprotectin was measured in asymptomatic FDRs aged 6–38 years; those with persistent elevation, defined as >70 µg/g in at least two separate tests, were offered panenteric video capsule endoscopy or ileocolonoscopy”

Population: 331 (35%) first-degree relatives (FDRs) (from a group of 950) agreed to be screened: 63 (19%) had persistently elevated calprotectin, of whom 42 underwent further evaluation

Key findings:

  • From the initial screened cohort of 331 patients, nine (2.7%) had endoscopic appearance compatible with presymptomatic CD, and 22 (6.6%) had non-specific macroscopic mucosal changes
  • Median calprotectin was significantly higher in those with presymptomatic CD (772µg/g (IQR 279–1685)) compared with others (31µg/g (IQR 30–61), p<0.0001)
  • Calprotectin >225 µg/g predicted presymptomatic CD (area under the receiver operating
    characteristic curve 0.97 (95% CI 0.94 to 1.0; p<0.001; sensitivity 89%, specificity 94%)

Discussion Points:

  • “There is no universally accepted definition for preclinical stages of CD, and
    the distinction between these stages remains partly subjective.”
  • “The lack of longitudinal follow-up is also a limitation, but this will be completed as part of the PIONIR trial.”

My take (borrowed in part from the authors):

  1. Identification of pre-symptomatic CD “can facilitate designing targeted interventions and defining inclusion criteria for prevention trials.” The disease may be more modifiable in the early stages of disease.
  2. This trial suggests the calprotectin threshold of >70 is too low to target screening. For specificity, the study showed that persistent elevation above 225 merits investigation; though, it has been our practice to use a threshold of >150 for children older than 5 years.
  3. Approximately 5% of asymptomatic FDRs of CD patients have evidence of pre-symptomatic CD and approximately 10% more have non-specific mucosal changes when evaluated

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How to Best Use Steroids for Inflammatory Bowel Disease

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JD Feuerstein et al. Clin Gastroenterol Hepatol 2025; 23: 2068-2082. Open Access! Appropriate Use and Complications of Corticosteroids in Inflammatory Bowel Disease: A Comprehensive Review

Steroids are commonly used and misused for inflammatory bowel disease. This article reviews best practices, steroid formulations/dosing, and potential complications.

  • For moderate to severe ulcerative colitis (in adults), the authors recommend treatment with 40 mg of prednisone daily. Patients with ASUC (acute severe ulcerative colitis) should be treated with 60 mg of IV methylprednisolone for 3 to 5 days, after which rescue therapy should be initiated
  • Use of budesonide is recommended as an option for many clinical situations to minimize steroid adverse effects. These situations include mild-moderate UC failing to respond to mesalamine, ileal CD and older patients
  • Postoperative complications: “In the postoperative period, patients treated with CS had a higher risk of both infectious complications (aOR, 3.69; 95% CI, 1.24–10.97) and major infectious complications (aOR, 5.54; 95% CI, 1.12–27.26) [Abrerra et al].135  Subramanian pooled data from 7 studies showing that preoperative CS use is associated with increased postoperative complications (OR, 1.41; 95% CI, 1.07–1.87) as well as infectious complications.

The authors note that corticosteroids “remain widely available and are an effective short-term option for induction of remission in patients with active UC or inflammatory CD. However, their well-described and significant safety profile warrants proactive strategies to limit their use through non-systemic formulations, short-term exposures, steroid-sparing maintenance options, and most recently, complete steroid avoidance strategies.”

My take: Continuing steroids when they are not effective prior to potential surgery (eg. ASUC) remains a frequent problem. Sometimes, it is difficult to know it they are helping some.

Understanding the Ileal Pouch in Inflammatory Bowel Disease and Familial Adenomatous Polyposis

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A Phillip et al. J Pediatr Gastroenterol Nutr. 2025;81:913–921. A narrative review of the ileal pouch in pediatric inflammatory bowel disease and familial adenomatous polyposis

Introduction: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) can be a life changing solution for a subset of pediatric inflammatory bowel disease (IBD) and familial adenomatous polyposis (FAP) patients. For patients with severe disease a three-stage approach is commonly performed.

Creation of IPAA -Three Stages:

Endoscopic Images and IPAA Anatomy:

  • The article provides guidance on complications including pouchitis, CD-like inflammation of the pouch, J-pouch failure, fertility after IPAA along with follow-up/screening recommendations.
  • As for screening, adult guidelines recommend annual screening for IBD patients with high risk features—previous dysplasia, primary sclerosing cholangitis, type C mucosa, refractory pouchitis. In those without these features, guidelines are variable, with one suggesting screening every 5 years. In FAP patients, the recommendation for surveillance screening following IPAA is pouchoscopy every 1–2 years.8

My take: Most pediatric gastroenterologists are not proficient in pouch management due to the small number of our patients needing IPAA. This review provides a terrific review/resource.

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Randomized Control Trial of the Modified Crohn’s Disease Exclusion Diet (CDED)

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RS Boneh et al. Clin Gastroenterol Hepatol 2025; 23: 2001-2011. Open Access! Modified Crohn’s Disease Exclusion Diet Maintains Remission in Pediatric Crohn’s Disease: Randomized Controlled Trial

In this “DIETOMICS” study with 56 children with mild-to-severe Crohn’s disease, after a 2 week exclusive enteral nutrition (EEN) diet, 30 patients were randomized to CDED and 26 to EEN.

Diet intervention: The CDED group followed 3 diet phases over 24 weeks: phase 1 (weeks 3–8) supplemented with 50% PEN; phase 2 (weeks 9–14) with 25% PEN, as described previously16; and phase 3 (weeks 15–24) with gradual introduction of more foods, including 1 and 2 free meals per week from weeks 15 and 18, respectively.17 Patients in EEN group received 8 weeks of EEN followed by gradual introduction of free diet with 25% PEN up to week 24.

Key findings:

This study with a relatively small number of enrolled patients had a lot of variables in dietary parameters. “An additional potential confounder in this study is the use of IMM therapy. Although both groups were recommended to initiate IMM therapy from weeks 4 to 5 to maintain remission, several CDED patients opted for monotherapy with CDED and preferred to delay medication initiation. Interestingly, 90% of patients on CDED without IMM therapy were in remission at week 14 and 100% were in remission at week 2” (possibly impacting decision not to use IMM).

My take: This study adds another piece of information to the puzzle on dietary therapy for Crohn’s disease. The authors note the following: “while CDED shows promise as a standalone therapy in some cases, in more severe cases it may be more appropriately as an adjuvant to top-down treatment with early anti-TNF.4 Recent research and guidelines advocate for a top-down approach (anti-TNF ± nutrition) for more severe disease, emphasizing the integration of anti-TNF therapy with nutrition.8,29 This approach is crucial during critical growth stages, as the conventional step-up method may lead to ineffective use of IMM with prolonged steroid exposure and growth issues.12“

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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

Proximal Ileal Crohn’s Disease is Harder to Treat

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K Takenaka et al. Clin Gastroenterol Hepatol 2025; 23: 1991-2000. Open Access! Inadequate Efficacy of Biologics for Treating Proximal Ileal Lesions in Crohn’s Disease: A Prospective Multicenter Study

This multicenter prospective study (n=253) examined efficacy of treatment in patients with proximal ileal disease using balloon-assisted enteroscopy (BAE). The recruited patients had a mean disease duration of 4 years. 52% were naive to biologic treatment at baseline.

Key findings:

  • At baseline, 74 patients (29.2%) had proximal ileal ulcerations without terminal ileal ulcerations
  • At week 26, after treatment with anti-TNF therapy (n=103), ustekinumab (n=99) or vedolizumab (n=51), endoscopic remission was achieved in 91 patients (36.0%). Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum
  • The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared with the colon (63.4%) and terminal ileum (56.7%)
  • After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P = .0126 for hospitalization and P = .0014 for surgery). In contrast, there was no significant differences in hospitalization and surgery associated with endoscopic activity vs remission in the colon or terminal ileum.

Discussion: Residual “proximal ileal ulcerations … are associated with a poorer prognosis…Additionally, we confirmed that proximal ileal inflammation is less responsive to biologic therapies compared with colonic inflammation. Although the reasons for this disparity remain unclear”

My take: Balloon-assisted enteroscopy is not frequently used in the setting of inflammatory bowel disease, particularly in pediatrics. MRE is typically used to follow proximal small bowel disease, though it has less sensitivity for luminal mucosal disease.

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Hypercoagulation with Acute Severe Ulcerative Colitis (ASUC) Persists for Months

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BJ Griffiths et al. Clin Gastroenterol Hepatol 2025; 23: 1798-1807. Open Access (PDF)! Hypercoagulation After Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study

Methods: In this prospective study, twenty-seven adult patients with ASUC and 25 control patients with quiescent ulcerative colitis were recruited. Thrombin generation (endogenous thrombin potential), rotational thromboelastometry (EXTEM and FIBTEM maximum clot firmness), procoagulant factors, anticoagulant factors, and fibrinolytic markers were assessed for those with ASUC on admission (Day 1), Day 5, 4 weeks, and at 8–12 weeks. These assessments were performed on a single occasion for control patients.

Key findings:

Discussion:

  • “Patients with ASUC had a hypercoagulable profile on initial presentation to the hospital, before receipt of LMWH, which was consistently demonstrated by individual and global assays of coagulation. The most marked elevations of individual factors at presentation were seen in the levels of Clauss fibrinogen, platelets, VWF, and FVIII, alongside heightened
    levels of the inhibitors of fibrinolysis PAI-1 and TAFIa.”
  • “This hypercoagulable state persisted for many weeks after hospital discharge, with levels of FVIII, fibrinogen, VWF, and inhibitors of fibrinolysis (TAFIa) remained significantly elevated at all timepoints up to 12 weeks, compared with the control population. This is despite
    intensive treatment for ASUC in all patients.”
  • “VTE and pulmonary embolism are 1 of the leading causes of morbidity and mortality during IBD flare-ups. The findings from this study reinforce the importance of thromboprophylaxis administration to all patients with ASUC at first presentation to hospital.”

My take: This study is in adults; the risk of VTE is lower in children and guidance on VTE prophylaxis is not clear.

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Prior Exposure to TNF Antagonists May Increase Response to JAK Inhibitors in Patients with Ulcerative Colitis

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HH Lee et al. Clinical Gastroenterology and Hepatology 2025; 23, 2102 – 2114. Open Access! Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists

Methods: Meta-analysis of 17 randomized controlled trials in 8871 adults with moderate-severe UC. The authors calculated the ratio of odds ratio of achieving remission with active drug vs placebo, in TNF antagonist–naïve vs TNF antagonist–exposed patients.

Key findings:

  • JAK inhibitors: Less efficacious in TNF antagonist–naïve vs exposed patients (6 trials; ratio of OR, 0.47)
  • IL-23 antagonists: No significant difference was observed in efficacy of selective interleukin-23 antagonists vs placebo in TNF antagonist–naïve vs exposed patients (6 trials; ratio of OR, 1.07)
  • Lymphocyte trafficking inhibitors: More efficacious in TNF antagonist–naïve vs exposed patients (5 trials; odds ratio [OR], 1.88)

Discussion:

  • This study “confirmed prior observations that exposure to TNF antagonists significantly reduces the efficacy of lymphocyte trafficking inhibitors in inducing remission, including both vedolizumab and S1P receptor modulators, by approximately 50%.In contrast, prior exposure to TNF antagonists was associated with a significant increase in the efficacy of JAK inhibitors in inducing remission, with 2-fold higher efficacy in TNF antagonist–exposed vs TNF antagonist–naïve patients”
  • In the SELECT-COMPARE trial in patients with rheumatoid arthritis, there was also an improved response to upadacitinib in patients with prior adalimumab.
  • “The current findings raise the intriguing possibility that exposure to TNF antagonists could result in lasting effects on the immune system that differentially alter responsiveness to therapies with distinct mechanisms of action”

My take: This study suggests that JAK inhibitors are a good choice for secondary therapy after anti-TNF agents. Other factors, besides efficacy, including safety, extraintestinal manifestations, and cost, have to be considered as well.

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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.

Comprehensive ACG Clinical Guidelines for Ulcerative Coliits (2025)

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D Rubin et al. The American Journal of Gastroenterology 120(6):p 1187-1224, June 2025. Open Access! ACG Clinical Guideline Update: Ulcerative Colitis in Adults

Today and tomorrow I am highlighting two adult clinical guidelines both of which are equivalent to up-to-date textbook chapters with specific recommendations; both are open access. In addition, the articles have accompanying author podcasts. Thanks to Ben Gold for these references.

Table 2 in the UC guideline makes 54 recommendations and Table 3 provides 57 key concepts.

Selected Management Recommendations:

  • Table 2, #4: We recommend treating patients with UC to achieve endoscopic improvement (Mayo score 0 or 1) to increase the likelihood of sustained steroid-free remission and to prevent hospitalization and surgery
  • Table 2, #5: We recommend the use of FC (fecal calprotectin) in UC to assess response to therapy, to evaluate suspected relapse, and during maintenance
  • Table 2, #33: When infliximab is used as induction therapy for patients with moderately to severely active UC, we recommend combination therapy with a thiopurine
  • Table 2, #43: Recommend continuing tofacitinib or upadacitinib as compared with no treatment for maintenance of remission in patients with prior moderately to severely active UC now in remission after induction with tofacitinib or upadacitinib. **The authors recommend continuing each biologic that achieved remission with induction therapy (#38-#43)
  • Table 2, #51: In patients with ASUC failing to adequately respond to intravenous corticosteroids (IVCS) by 3 days, we recommend medical rescue therapy with infliximab or cyclosporine (Strong recommendation, moderate quality of evidence).

Key concepts:

  • Table 3, #29: Patients who are primary nonresponders to an anti-TNF (defined as lack of therapeutic benefit after induction and despite sufficient serum drug concentrations) should be evaluated and considered for alternative mechanisms of disease control (e.g., in a different class of therapy) rather than cycling to another drug within the anti-TNF class.
  • Table 3, #31:  Subcutaneous infliximab and vedolizumab are considered equivalent to the standard intravenous maintenance dosing of these agents. The equivalence of the subcutaneous formulations for induction or as substitution for escalated doses of these therapies has not been robustly established.
  • Table 3, #41: Patients with UC should have available all medical options as recommended by their doctor and healthcare team. Third-party payers and requirements for step therapy should not come between the patient and their healthcare team in making decisions about treatment for UC.
  • Table 3, #48: All patients with ASUC should undergo a flexible sigmoidoscopy within 72 hours and preferably within 24 hours of admission. This should be used to assess endoscopic severity of inflammation and to obtain biopsies to evaluate for cytomegalovirus (CMV) colitis.
  • Table 3, #51: Nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics, and medications with anticholinergic side effects should be avoided in ASUC.
  • Table 3, #57: In patients with ASUC initiating infliximab, dose intensification should be considered for those patients with low serum albumin (<2.5 g/dL).

My take: This article does an excellent job of summarizing current available evidence and good practice. Many of the recommendations may be helpful in garnering approval from third party payers.

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