Tag Archives: Ulcerative colitis

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

Chronic Nonbacterial Osteomyelitis Associated with Pediatric Inflammatory Bowel Disease

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M Matar et al. J Pediatr Gastroenterol Nutr. 2026;82:487–494. Chronic nonbacterial osteomyelitis associated with pediatric inflammatory bowel disease: : A multicenter retrospective study from the Paediatric inflammatory bowel disease Porto Group of ESPGHAN

Methods: Retrospective study with 45 pediatric patients with inflammatory bowel disease (n=32 with Crohn’s disease, n=8 with ulcerative colitis, n=5 with IBD-U)

Key findings:

  • CNO presented in 15 patients (33%) within 3 months of IBD diagnosis, and in additional 20 (44%) patients after IBD diagnosis; in 10 (22%) patients CNO preceded the diagnosis of IBD with a median time 46 (25–248) weeks
  • 11 (24%) subjects displayed at least one additional extra-intestinal manifestations, including arthritis (6, 13%), erythema nodosum (4, 9%), sacro-ileitis (2, 4%), psoriasis (1, 2%), and pyoderma gangrenosum (1, 2%).
  • Complications occurred in six patients and included vertebral collapse, bone fracture, and bone deformity. In eight (18%) subjects vertebral collapse was present already at the time of diagnosis.
  • “While in most patients, diagnosis of CNO was associated with either clinical or laboratory indices of active IBD, especially CD, in some cases, the intestinal disease was quiescent.”
  • “All patients achieved remission of CNO at some point during follow-up, which may support the hypothesis that anti-TNF treatment is unlikely to promote CNO development and does not reinforce the theory of a paradoxical effect that has been suggested by Cordesse et al.22“

My take: This is a useful review highlighting the association of CNO with both active disease and quiescent IBD. The authors argue that their data does not support the development of CNO as a paradoxical effect. I disagree with this premise. Many of the extraintestinal manifestations, that anti-TNF agents can treat, rarely can be caused by them. Besides CNO, paradoxical reactions to anti-TNF agents have included the development of rheumatoid arthritis, psoriasis, hidradenitis suppurativa and autoimmune liver disease.

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How to Improve the Value of Biologic Infusions: Reduce Lab Testing and Frequency

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T Shah et al. JPGN Reports 2026;1–5. Responsible laboratory surveillance of pediatric patients with inflammatory bowel disease on biologic infusion therapy

This retrospective single-center study with 34 pediatric patients with inflammatory bowel disease examined the laboratory costs (2020-2021) associated with monitoring biologic therapy.

Methods: “Routine laboratory studies were defined as those part of the standardized infusion protocol at SBCH and were obtained with each scheduled infusion. The following laboratory studies were considered routine/standard: complete blood count with differential, basic metabolic panel, liver function tests, amylase, lipase, erythrocyte sedimentation rate, C-reactive protein, vitamin D, iron, ferritin, vitamin B12, folate, urine hCG (if a subject was female). Other laboratory studies that were collected, but not considered routine studies included QuantiFERON-TB, and biologic drug and antibody level.”

Key findings:

  • The average hospital charge for studies obtained per infusion was $1308.36 with an average annual cost of $9543.44 per patient
  • Fifteen (6%) instances of change in clinical management were found. “Only a limited subset of the 15 laboratory studies included were utilized in making changes: biologic drug, Vitamin D, and iron level”
  • During the study, 248 infusions were administered with a “total annual charge amongst all patients in the study was $324,447”

Discussion:

  • “Our study population had well controlled disease as evident by low PCDAI and PUCAI scores…Our observations suggest the utility of routine laboratory surveillance at each biologic infusion is minimal, favoring decreased testing for IBD patients, especially those in clinical remission.”
  • “We propose obtaining laboratory tests twice a year, or with every third infusion, for patients with mild disease or in remission based on their disease activity index scores. In our small cohort of patients, this change in practice would reduce the total annual costs by 66% ($214,154.82)”

My take: It has been my practice, for most patients with IBD, to obtain labs with every other infusion (~3 times per year). Typically, I will obtain a CBC/d, CMP and CRP and obtain other labs like Vit D, GGT, Quantiferon Gold and drug level monitoring less frequently. I rarely check Vit B12, ESR, Folate, Amylase, and Lipase.

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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.

Afimkibart for Ulcerative Colitis (TUSCANY-2)

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S Danese et al. The Lancet Gastroenterology & Hepatology 2025; 10: 882 – 895. Anti-TL1A antibody, afimkibart, in moderately-to-severely active ulcerative colitis (TUSCANY-2): a multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b trial

Briefly noted:

Methods: “The multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b, TUSCANY-2 trial” enrolled 228 people who completed induction. All patients had moderate to severe ulcerative colitis who were treated with either subcutaneous afimkibart (a TNF-like ligand 1A (TL1A)) or placebo. There was a 12-week induction phase followed by a 40-week maintenance phase.

Key findings:

  • At week 14, the primary endpoint of clinical remission by total Mayo score was reported in 12 (26%) of 47 patients in the afimkibart 50 mg group, 14 (23%) of 60 patients in the afimkibart 150 mg group, and 21 (24%) of 88 patients in the in the afimkibart 450 mg group versus five (12%) of 43 patients in the placebo group
  • Incidences of treatment-emergent adverse events during induction were similar with placebo and afimkibart
  • The percentages of remission were higher for every afimkibart dose but this did not reach statistical significance compared to placebo

My take: Further testing is needed to determine whether afimkibart will have a significant place for treatment of inflammatory bowel disease.

Iguazu Falls

VedoKids Study: Vedolizumab for Extraintestinal Manifestations of Inflammatory Bowel Disease

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G D’Arcangelo et al. J Pediatr Gastroenterol Nutr. 2026;82:495–502. Open Access! Vedolizumab for extraintestinal manifestations in pediatric inflammatory bowel disease: Results from the VedoKids study

Background: “Since vedolizumab is a gut-selective anti-α4β7 integrin, its effect on EIMs has been a matter of debate, with relevant data lacking in pediatric IBD. A systematic review, which included three interventional studies, five non-interventional studies, and three case series, concluded that there is insufficient evidence supporting the efficacy of vedolizumab for treating pre-existing EIMs in adults.3“

Methods: This was a subgroup analysis of the pediatric VedoKids cohort, a multicenter, prospective “real-life” study of children (aged 0–18 years) with IBD treated with vedolizumab and followed through 54 weeks.

Key findings:

  • EIMs were identified in 18/142 (12.6%) children at baseline
  • Children with EIMs had an average age of diagnosis of 9 yrs compared to 12 yrs in those without EIMs
  • Children with EIMs had higher rate of pancolitis in UC and ileocolonic distribution in CD
  • Prior anti-TNF medication was noted in 16 (89%) of EIM cohort compared to 74 (60%) of non-EIM cohort
  • Concomitant medications were administered in 72% of EIM cases and to a similar number of non-EIM patients. For EIM patients, ASA were given in 7, steroids in 10, thiopurines in 4 and methotrexate in 2
  • Children with EIMs had more active disease (see below)
  • EIM resolution rate of 89%, mainly occurring within the early weeks of vedolizumab treatment

My take: While this study has several limitations, including the high rate of concomitant medications, it shows that most patients receiving vedolizumab had resolution of their EIMs. In addition, it shows that patients with EIMs had a more severe IBD phenotype.

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