Category Archives: inflammatory bowel 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

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

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

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

    Key findings:

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

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

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

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

    Related blog posts:

    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

    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

    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.

    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.

    Related blog posts:


    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

    Related blog posts:

    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.

    Related blog posts:

    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“

    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