Tag Archives: Ulcerative colitis

Comparative Safety of Advanced Therapies for Ulcerative Colitis

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D Ahuja et al. Am J Gastroenterol 2026;121:1192–1201. Comparative Safety of Advanced Therapies in Patients With Ulcerative Colitis: An Administrative Claims-Based Study

Methods: Using an administrative claims database (OptumLabs Data Warehouse) with a ‘real-world’ cohort, the authors identified 9,430 patients with UC treated with TNF antagonists (n = 4,111), anti-integrins (n = 3,165), anti-ILs (n = 1,342), JAK inhibitors (n = 701), or sphingosine-1 phosphate receptor modulators (n = 111), followed over median 27 months.

Key findings:

Overall, the risk of serious infections was higher with infliximab than with the other therapies. The incidence of VTE in patients with UC was very low and comparable across all advanced therapies, including JAK inhibitors. Also, the incidence of MACE in patients with UC was
very low and comparable across all advanced therapies, including anti-ILs and JAK inhibitors.

From the discussion: “In a recent network meta-analysis and corresponding clinical guidelines on the management of moderate-to-severe UC, upadacitinib was ranked as having the highest efficacy for induction ofremission compared with all other agents (2,14). However, safety concerns with JAK inhibitors were raised in the pivotal ORAL Surveillance trial (15). In this noninferiority trial, tofacitinib, particularly at higher doses, was associated with a higher risk of serious and opportunistic infections, VTE, and MACE, compared with TNF antagonistsi n patients with rheumatoid arthritis. Following this, the US Food and Drug Administration changed JAK inhibitors’ labeling across all indications, restricting its use in patients with previous failure or intolerance to TNF antagonists…the ORAL Surveillance trial focused on older patients aged 50 years or older with rheumatoid arthritis and at least one cardiovascular risk factor…

[In this study, the] lack of an apparent increase in the risk of JAK inhibitors compared with other medications may be related to superior disease control achieved with JAK inhibitors or reverse causality where patients at high risk of MACE and/or VTE events are not prescribed JAK inhibitors.”

My take: This study provides additional reassurance that newer advanced therapies have similar or better safety than infliximab.

Related blog posts:

Don’t Rush to Judge Risankizumab Effectiveness for Ulcerative Colitis

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R Panaccione et al. Clin Gastroenterol Hepatol 2026; 24: 1424-1433. Open Access! Impact of Extended Risankizumab Treatment in Patients With Ulcerative Colitis Who Did Not Respond to Induction Treatment

Methods:

  1. In the AbbVie-funded phase 3 INSPIRE induction study, 209 initial nonresponders to 12 weeks of 1200 mg intravenous (IV) risankizumab induction were rerandomized to receive 12 weeks of additional 1200 mg risankizumab (weeks 12, 16, and 20) or 180 mg or 360 mg subcutaneous [SC] risankizumab (weeks 12 and 20) in a double-blind fashion
  2. Then, the delayed responders continued to receive blinded risankizumab at their assigned dose in the phase 3 COMMAND maintenance study
  • Clinical response per adapted Mayo Score (AMS): decrease from baseline ≥2 points and ≥30% from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1
  • Clinical remission per AMS: SFS ≤1 and not greater than baseline, RBS = 0, and endoscopic subscore ≤1 without the evidence of friability

Key findings:

  • Initial nonresponders (1200 mg IV [n = 68], 180 mg SC [n = 71], or 360 mg SC [n = 70]) had week 24 clinical response rates of 50%, 56.3%, and 57.1%, respectively
  • Patients also achieved clinical remission, histologic endoscopic mucosal improvement (8.8%, 12.7%, and 15.7% for both endpoints), endoscopic improvement (17.6%, 18.3%, and 24.3%), and endoscopic remission (1.5%, 8.5%, and 5.7%)

My take: A longer trial of risankizumab is often needed to know with certainty if it will work for ulcerative colitis. More than half of initial nonresponders acquire a clinical response with extended therapy. A similar pattern was noted for risankizumab with Crohn’s disease.

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

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

    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.

    Related blog posts:

    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

    Related blog posts:

    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.

    Related blog posts:

    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.”

    Related blog posts:

    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.

    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.

    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.”

    Related blog posts: