Tag Archives: Ulcerative colitis

Mirikizumab for Pediatric Ulcerative Colitis

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K Jimbo et al. Inflammatory Bowel Diseases 2026; 32: 711-720. Real-World Effectiveness of and Optimization Strategies for Mirikizumab in Pediatric Ulcerative Colitis: A Prospective, Observational Study

Methods: This prospective cohort study included Japanese children (n=28) with UC receiving intravenous mirikizumab (300 mg at weeks 0, 4, 8), followed by subcutaneous maintenance (200 mg every 4 weeks). The cohort had a median age 13 years (50% female) with a median PUCAI 67.5; 67.4% were biologics-naive. In those with clinical remission at 12 weeks, sucutaneous injections were started; otherwise, IV infusions (prolonged induction, n=11) continued every 4 weeks. Complete remission was defined as PUCAI<10 and colonic wall thickness on IUS <3.0 mm with no detectable color Doppler flow signal throughout the colon.

Key findings:

  • The median time to complete remission (CR) was 10 weeks. All patients ultimately achieved CR
  • Durable CR was achieved in 27/28 (96%).
  • SF-CR generally increased over time: 17/28 (61%) at week 12, 28/28 (100%) at week 24, and 27/28 (96%) at wek 52
  • No serious adverse events were noted. 6 children developed self-limiting flu-like symptoms

Limitations included relatively small number of patients at a single center. Also, the majority of patients had not received prior advanced therapies.

My take: It is encouraging to see favorable pediatric data. Though, the complete remission rate of 100% will likely be an outlier as more data become available.

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ImmunogenicityTable by Tauseef Ali IBD Library

Development of a Standardized Care Transfer Summary

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J Tung et al. J Pediatr Gastroenterol Nutr. 2026;82:1057–1061. Development and testing of a pediatric inflammatory bowel disease medical transfer summary

This article describes a “multidisciplinary development and testing of a standardized pediatric IBD medical transfer summary template (PIBD-MTS) as a tool to improve the handoff of patient care.”

The “succinct nature allows AGIs [adult GIs] to review information within 10 min, in contrast to typically sifting through copious disorganized notes that may be redundant, at times irrelevant or missing key information. Its comprehensive nature includes prompts for disease monitoring, health maintenance, nutrition as well as mental health and socioeconomic factors that may affect IBD care.”

My take: This is a good template for transitioning patients. Though the focus is on transfers to adult gastroenterologists as patients get older, this form would be applicable for many patients who see other pediatric gastroenterologists for location or second opinions. It would be a good idea for this form to be available on the ImproveCareNow website. (It may be there but I did not see it). In addition, many centers may want to incorporate this template into their EMRs (eg. EPIC letter).

Link: ImproveCareNow

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The transfer template is accessible as a word document (supplement 1) at the end of the report. Here is a screenshot:

Dr. Bonney Reed: Optimizing Quality of Life in IBD

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We had a terrific lecture given to our group by Dr. Bonney Reed. She is a pediatric psychologist with a clinical and research focus on children with inflammatory bowel disease. Our group has worked closely with Dr. Reed for many years. Many of her slides are included below along with my notes; my notes may contain errors in transcription and in omission.

  • GI symptoms may begin as the result of organic disease (e.g., IBD). Anxiety and chronic activation of the stress response system may lead to alterations in the brain, spinal cord, and gut increasing the load of GI symptoms. In turn, distress associated with GI symptoms may contribute to anxiety or depressed mood, creating a cycle of worsening GI symptoms and overall psychological distress.
  • Consistent with a brain-gut axis model, individuals with IBD, compared to healthy controls, demonstrate dysfunction of the ANS indicative of a chronic stress response which is characterized by increased sympathetic nervous system (SNS) activity and reduced parasympathetic nervous system (PNS) activity
  • Psychological factors are the key factor for pediatric patients with IBD when self-rating their global health
  • Factors that contribute to an individual’s current QoL: symptom exacerbation, psychological functioning including stress, and family support.
  • Health-related quality of life factors: major life transitions (eg. graduating high school and needing to manage IBD at college), fatigue ( persists despite controlled inflammation), poor body image (especially with weight changing rapidly), a diminished self-perception or seeing oneself as less capable, comorbid functional abdominal pain (about a quarter of youth with IBD), and food restrictions that can interfere with daily quality of life.
  • Stress plays important role influencing (bidirectional) disorders of brain gut interaction (DBGI)
  • Dr. Reed’s research includes a longitudinal cohort of newly-diagnosed (w/in 45 days) pediatric patients with IBD. This cohort undergoes psychosocial assessment along with ANS assessment
  • Emotional reactivity indicates individuals with a ‘short fuse’ who take longer to return to normal.  Those with emotional reactivity are at increased risk for anxiety/depression.
  • Skin conductance response (SCR) can help determine autonomic nervous system (ANS) dysfunction.  It is a measure of sympathetic arousal and stress
  • Stressful life events increase the rates of depression and correlate with skin conductance at medium and high levels
  • Within this model, Dr. Reed’s research focuses on the hypothesis that autonomic dysfunction is indicative of a chronic stress response. This, in turn, contributes to increased sympathetic nerve activity and decreased parasympathetic activity. This contributes to symptoms of anxiety and depression as well as GI clinical symptoms, all of which lead to impairments in QoL. Addressing autonomic dysfunction may provide a mechanism by which to address all of these QoL drivers
  • ANS dysfunction (which is also seen in cyclic vomiting syndrome) can improve with biofeedback focused heart rate variability (HRV). HRV, in turn, is associated with increase inflammation
  • Preliminary data from breath pacer intervention has shown in improvement in multiple variables

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Genetic Risk Impacts Severity of Inflammatory Bowel Disease

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MV Vestergaard et al. Gastroenterol 2026; 170: 721-734. Open Access! Genetic Risk of Inflammatory Bowel Disease Is Associated With Disease Course Severity

Methods: The authors calculated IBD polygenic scores (PGS) for 3732 Danish patients with Crohn’s disease (CD) and 4535 patients with ulcerative colitis (UC), and investigated their association with disease outcomes.

“The Danish National Biobank stores neonatal blood spots from almost all Danes born since 1982…The North Denmark IBD (NorDIBD) cohort is a population-based cohort of all patients from the North Denmark Region with a confirmed IBD diagnosis from 1978–2020.17 From this cohort, 940 patients with IBD and a further 973 blood donors with no IBD diagnosis were genotyped from whole blood…applied variant loadings for calculating PGS for CD and UC susceptibility generated by Middha et al19 to our dataset. These variant loadings were derived from summary statistics from the IIBDGC.” This cohort had a young age. Only 2% and 3% of CD and UC patients, respectively, were 40+.

Severe Disease Definitions:

  • For patients with CD, a severe disease course was defined as experiencing (1) 2 or more IBD-related hospitalizations exceeding 2 days, (2) 2 or more IBD-related major surgeries, (3) 1 IBD-related hospitalization and 1 IBD-related major surgery not overlapping in time, or (4) a total use of at least 5000 mg prednisolone-equivalent systemic corticosteroids within the first 3 years after diagnosis
  • For patients with UC the severity definition was modified to experiencing (1) 2 or more IBD-related hospitalizations exceeding 2 days, (2) 1 or more IBD-related major surgeries, or (3) a total use of at least 5000 mg prednisolone-equivalent systemic corticosteroids. 

Key findings:

  • Increased PGS was associated with higher fecal calprotectin and C-reactive protein levels, and decreased hemoglobin levels
  • When comparing the highest vs lowest PGS quintile, we observed a hazard ratio for major surgery of 2.74 in patients with CD and of 2.04 in UC
  • Patients with severe disease had higher PGS than patients with less severe disease (CD, odds ratio = 1.25; UC, odds ratio = 1.33)

The graphs below show the differences in hospitalization and surgery based on PGS for CD (A & B) and then for UC (C & D)

Discussion:

  • “Our results suggest that IBD susceptibility genetics only explain part of the severity of IBD, hence leaving room for other factors at play… This observation is promising, as it points toward the possibility of modulating the effects of genetic susceptibility through lifestyle interventions directed toward potential environmental factors that are yet to be uncovered.”

My take: It is intuitive that those with more genetic risk factors would be more likely to have severe disease. This study shows this assumption is correct in this cohort; in fact, there is a dose-response relationship. Those with higher PGS had more hospitalizations, major surgeries and medical treatments.

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Position Paper: Expediting Drug Approval for Pediatric IBD

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D Turner et al. J Pediatr Gastroenterol Nutr. 2026;82:867–894. Reshaping study design for faster extrapolation‐baseddrug approval in pediatric inflammatory boweldiseases: An ESPGHAN–NASPGHAN position paper

“It has been 11 years since the adult approval of vedolizumab and 9 years since the approval of ustekinumab, yet neither is currently approved for use in children (Table 1). Instead of taking the necessary steps to shorten this unacceptable delay, there are now extra hurdles for clinical trials such as three ileocolonoscopies over 1 year in both pediatric CD and UC, as suggested by the FDA…”

Addendum: See comment by Matthew Kowalik, MD who is the Director (Acting) of Division of Gastroenterology for FDA/CDER/OND/OII. There has been recent approval recent of Stelara (ustekinumab) for the treatment of pediatric patients 2 years and older with moderately to severely active Crohn’s disease. Here’s a link: Johnson & Johnson (JNJ) Gains FDA Approval for Pediatric Crohn’s Disease Treatment

“Pediatric extrapolation is based on assessing relevant similarities in disease characteristics, drug pharmacology, and treatment response between the target pediatric population and adults or other reference pediatric populations. While, historically, extrapolating safety data was considered unacceptable, the recent International Council for Harmonization (ICH) E11A Guideline on pediatric extrapolation that has been endorsed in 2024 by the EMA”[European Medicines Agency (EMA) ]

Selected Summary Statements (total of 24 are in the report):

  • 1.There is no evidence that differences in pathogenesis and pathobiology between pediatric and adult patients with IBD are associated with differences in response to pharmaceutical therapies, except for monogenic disease (agreement 21/22).
  • 2.In general, efficacy and drug-related safety outcomes in children older than 2 years are comparable to adults (agreement 22/22).
  • 9. Optimal dosing should be used in all study arms in pediatric trials. Placebo, sham, or doses demonstrated to be subtherapeutic in prior studies should not be permitted. They are unethical in children, reduce feasibility of enrollment, and are not expected to be informative given the underpowered sample size of pediatric studies (agreement 22/22).
  • 13.Ileocolonoscopic assessment is the gold standard for assessing mucosal healing (MH) and should be required at most twice in each study: that is, at baseline and study end (agreement 22/22).
  • 14. Noninvasive objective measures, including serum and fecal biomarkers, magnetic resonance enterography (MRE), and/or intestinal ultrasound (IUS), should be used for assessing postinduction interim therapeutic response between the two ileocolonoscopies rather than requiring a third ileocolonoscopy (agreement 22/22).

My take (borrowed from the authors):

  • “While it is paramount to achieve a precise and comprehensive approval process for new drugs in pediatric IBD, it is equally important to expedite the process, so children and adolescents are not denied effective treatment available for adults with IBD…”
  • “Under these assumptions, future trial designs should be single-arm and open-label to focus on dosing and pharmacokinetics in children weighing <30–40 kg while mandating long-term safety registries, disease- and not necessarily drug-specific. Data should be supported by meticulously collected real-world evidence. Pediatric data must be collected as soon as a confident signal of efficacy and safety is achieved in adult studies…”
  • “This will resolve the current paradox in which children have the most severe and extensive disease and the highest efficacy of drugs, yet very limited access to these drugs.”

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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.

Comparative Safety of Janus Kinase Inhibitors vs Tumor Necrosis Factor Antagonists For Inflammatory Bowel Disease Patients

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D Ahuja et al. Clin Gastroenterol Hepatol 2026. 24: 794-804. Comparative Safety of Janus Kinase Inhibitors vs Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases

Methods: This retrospective cohort study used an administrative claims database and identified patients with IBD who were new users of either JAK inhibitors (n=856) or TNF antagonists (n=9422) between 2016 and 2023. Mean age was 45 years.

Key findings:

  • There was no difference in the risk of VTE (1.3 vs 1.2; HR, 0.66; 95% CI, 0.28–1.57) and MACE (0.4 vs 0.7; HR, 0.50; 95% CI, 0.19–1.30)
  • There was no difference in the risk of serious infections (4.9 vs 5.4; HR, 0.97); however, JAK inhibitors were associated with an increase risk of overall infections (incidence rate, 62.4 per 100 person-years [PY] vs 37.4 per 100 PY; hazard ratio [HR], 1.60)

The authors note that their findings differ from the ORAL study (Ytterberg et al. NEJM 2022; 386: 316-326.) which showed higher risk of MACE in patients receiving tofacitinib. In the current study, even in patients deemed to be at higher risk for MACE (age >50 years with at least 1 cardiovascular risk factor), JAK inhibitors were associated with lower incidence and risk of MACE compared with TNF antagonists (IR per 1000 PY, 0.4 vs 2.1, HR 0.10).

My take (borrowed from the authors) “It is unlikely that JAK inhibitors are associated with higher risk of VTE and MACE compared with TNF antagonists in most patients with IBD.”

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“Real-World” Experience: High Dose Upadacitinib Recaptures IBD Response

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AHY Ho et al. Clin Gastroenterol Hepatol 2026; 24: 763-771. Real-world Experience of Upadacitinib Reinduction and High-dose Maintenance Therapy in Inflammatory Bowel Disease

Methods: This was a prospective cohort study of patients (n=181 — 79 CD, 83 UC, 6 -IBD-U, 13 with IPAA) treated with UPA between April 2022 and November 2023. Included patients responded to UPA induction, had loss of response (LOR) after dose reduction, and subsequently received reinduction therapy with 45 mg QD. They were followed for a median duration 93 weeks.

Key findings:

  • Dose escalation to 45 mg QD for a median of 13 weeks (IQR, 8–36 weeks) recaptured clinical response in 80.4%
  • Among patients who recaptured response, 19 again reduced dose
  • 93.8% of patients on 45 mg QD maintained remission vs 21.1% who again dropped to 30 mg QD (P < .001)
  • Acne/rosacea was the most common adverse event (39%); there were no serious adverse events

In their discussion, the authors note that dose escalation with another JAK inhibitor, tofacitinib, also has been shown to reverse LOR (in about 50%). In addition, they note that “in our experience, prolonged exposure to 45 mg QDD UPA is safe.” Though, “a longer follow-up period…is required to address long-term safety of UPA in IBD, especially at a higher dose.”

My take: Many patients taking UPA have not responded to multiple other advanced therapy. As such, the potential to recapture response with a higher dose of UPA is an important finding. Dose intensification is an effective strategy for most of the advanced therapies.

Briefly noted: S Honap et al. Clin Gastroenterol Hepatol 2026; 24: 784-793. Open Access! Comparative Effectiveness of Tofacitinib vs Upadacitinib for the Treatment of Acute Severe Ulcerative Colitis In this retrospective study of 111 adults with ASUC, Between days 3 and 7 after treatment initiation, upadacitinib was associated with greater response rates (84% vs 54%), but response/remission was comparable at day 98 (45%/36% vs 55%/48%) and day
182 (29/29% vs 39/34%).

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How to Score the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Properly

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J Blackwell et al. Gastroenterol 2026; 170: 452-455: Open Access! A Normal UCEIS Is Zero: A Score Divided by a Common Language

“The index uses a Likert scale of vascular pattern, bleeding, erosions and ulcers, with a total score intended to reflect severity of disease. When the index was first published, the baseline score for each descriptor was 1, meaning that a normal vascular pattern, no bleeding, and no erosions or ulcers scored 3. However, when the index was subsequently validated, the values attributed to each descriptor were rebased to 0, to improve clinical utility…This means that a completely normal flexible sigmoidosopy scored 0 rather than 3, and the worst activity of UC ever seen by the investigators (compared with a visual analogue scale 0 to 100) was 8 rather than 11…

The UCEIS has since been shown to predict the need for escalation of medical treatment and has recently been incorporated into a validated prognostic clinical index to predict response to intravenous steroids among patients with acute severe UC.10,11 Accurate scoring is therefore essential, with direct implications for clinical decision making.”

My take: The UCEIS is more detailed than the Mayo score. However, I expect that before long artificial intelligence will be able to review images and give a more consistent interpretation of the severity of endoscopic findings than either of these scoring systems.

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Oral Integrin Inhibitor for Moderate to Severe Ulcerative Colitis

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BE Sands et al. Clin Gastroenterol Hepatol 2026; 23: 525-534. Open Access! A Phase 2 Study of MORF-057, an Oral α4β7 Integrin Inhibitor in Moderately to Severely Active Ulcerative Colitis

Background: MORF-057 is an orally administered small-molecule drug that inhibits α4β7 integrin-mediated recruitment of α4β7-expressing lymphocytes to the gut. It has a similar target as vedolizumab, a monoclonal anti-integrin antibody used to treat ulcerative colitis (approved in 2014), but it requires parenteral administration.

Methods: This open-label, phase 2a, single-arm, multicenter trial (EMERALD-1) comprised a 6-week screening period, a 52-week active treatment period (including a 12-week induction period and 40-week maintenance period), and a 4-week safety follow-up period. Of the 35 participants enrolled in the main cohort, 18 participants received 100 mg of oral MORF-057 twice daily for the entire treatment period.

The primary efficacy endpoint was a change in the Robarts Histopathology
Index (RHI) score from baseline to week 12. “RHI was chosen as the primary efficacy assessment because it is an objective measure that can be assessed in a blinded fashion, which was critical given the open label study design. RHI also allows for a deeper, more quantitative probe than endoscopy.”

Key findings:

  • MORF-057 was well tolerated, and no treatment-emergent serious adverse events were
    observed
  • At week 12, participants (n= 35) exhibited a mean change from baseline in RHI
    score of ‒6.4 (standard deviation, 11.2). Additionally, 22.9% of participants (8/35) achieved
    RHI remission (RHI score ≤3)
  • In participants with evaluable data (n=18), the effects of MORF-057 on pharmacokinetics, pharmacodynamics, and clinical efficacy were achieved at week 12 and remained consistent to week 52
Symptomatic remission based on whether patient was advanced therapy (AT)-naive or AT-experienced

My take: This small open label study shows that an oral medication targeting α4β7 integrin has potential as an effective therapy for ulcerative colitis. If effective, then it would be important to understand how it compares to vedolizumab.

Related blog post: In Trials: An Oral IL-23 Antagonist Peptide