Tag Archives: Ulcerative colitis

Constipation Preceding a New Diagnosis of Inflammatory Bowel Disease

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S Cenni et al. J Pediatr Gastroenterol Nutr. 2025;80:799–806. The prevalence of constipation in children with new diagnosis of inflammatory bowel disease: A retrospective study

This was a cross-sectional observational study in pediatric IBD-patients (n=238) with 104 (43.6%) with Crohn disease (CD), 130 (54.6%) with ulcerative colitis (UC) and 4 (1.6%). Only patients who filled out the Rome IV questionnaire for FC, through dedicated symptom recall at the next clinic appointment or telephone recall, were finally enrolled in the study for subsequent analysis.

Key findings:

  • Forty-seven out of 238 (19.7%) had a functional constipation history before the IBD diagnosis. In the CD children the prevalence of constipation before the IBD diagnosis was 19/104 (18.2%) and in the UC patients was 28/130 (21.5%).
  • The difference in terms of endoscopic localization was statistically significant in UC patients presenting FC (p = 0.026) with a prevalence of proctitis and left side colitis (30% and 15%, respectively)
  • There was a delay in the diagnosis of patients with preceding constipation

Discussion Points:

  • The main limitations of the present study are certainly related to the retrospective nature and, therefore, the possibility of recall biases must be taken into account.
  • Rectal bleeding that persists despite stool softener therapy should be investigated

My take: While this study shows that constipation is fairly common prior to a diagnosis of IBD, many times a parent is told that their child is constipated on the basis of an xray or simply because the child complained of stomach pain. This likely increases the risk of recall bias. My guess is that a prospective study involving careful questioning at the time of the initial colonoscopy would yield a lower number of children who had constipation at the time of diagnosis.

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Set of Shucked! at The Fox Theater. Really enjoyed this ‘corny’ musical.

Long-term Efficacy and Safety of Upadacitinib for Ulcerative Colitis

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R Panaccione et al. The Lancet Gastroenterology & Hepatology. 2025; 10: 507 – 519. Open Access! Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study

Methods: U-ACTIVATE is an ongoing, 288-week, phase 3, long-term extension study that enrolled patients (n=369) aged 16–75 years with a confirmed diagnosis of moderately to severely active ulcerative colitis; patients who had a clinical response in the induction studies were eligible to enter the U-ACHIEVE maintenance study. Patients not in clinical remission originally randomly assigned to upadacitinib 15 mg were eligible to escalate to upadacitinib 30 mg, those originally randomly assigned to upadacitinib 30 mg continued on upadacitinib 30 mg, and those originally assigned to placebo were eligible to escalate to upadacitinib 15 mg in a masked way

Key findings:

  • In the as-observed population, 84 (71%) of 118 patients receiving upadacitinib 15 mg were in clinical remission at week 48, as were 130 (67%) of 193 receiving upadacitinib 30 mg
  • By week 96, 69 (76%) of 91 patients receiving upadacitinib 15 mg and 104 (74%) of 141 of those receiving upadacitinib 30 mg were in clinical remission
  • The most common adverse events of special interest were hepatic disorder, lymphopenia, creatine phosphokinase elevation, serious infection, neutropenia, and herpes zoster
mNRI indicates modified non-responder imputation analysis response

My take: This study shows a good durable (3 year) response to upadacitinib treatment with both 15 mg and 30 mg dosing.

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    When an Inflammatory Bowel Disease Diagnosis is Far Away

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    JF McLaughin et al. Clin Gastroenterol Hepatol 2025; 23: 825-834. Travel Time to Treating Center Is Associated With Diagnostic Delay in Pediatric Inflammatory Bowel Disease

    This was a cross-sectional study of newly diagnosed pediatric patients (n=869) with IBD at 22 United States sites from 2019 to 2022. 57% were diagnosed with CD, 34% with UC, and 4% with IBD-U.

    Key findings:

    • Overall, the mean time from symptom onset to diagnosis was 265.9 days
    • Factors associated with longer diagnosis time included CD vs UC (odds ratio [OR], 2.6), and longer travel time to clinic (>1 hour [OR, 1.7], >2 hours [OR, 1.8] each vs <30 minutes)
    • There was no association with race, ethnicity, birth country, gender, parent education, household income, insurance type, health literacy, and health system distrust

    The finding that there is a longer diagnostic delay with CD than UC is consistent with prior studies. The longer travel time has not been widely recognized as a factor associated with delayed diagnosis, though it has been associated with other negative outcomes like higher mortality with chronic liver disease.

    Regarding the lack of a negative impact from factors like race/ethnicity and income, my suspicion is that this is probably related to several factors:

    • Overall, the pediatric age group has a very high rate of being insured as most children without commercial insurance currently qualify for Medicaid. This helps improve access to needed/timely health care
    • A recent study showed that pediatric GI specialists do not have disparities in treatment compared to pediatric GI providers with an IBD focus; thus, pediatric specialists are more likely to minimize treatment delay (Treatment Disparities in Adult vs. Pediatric IBD Care Related to Provider Specialization)
    • Parents help limit diagnostic delay in their children

    My take: There are many places that are far away from pediatric specialists. This results in diagnostic delays.

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    Cholangiocarcinoma Risk in Pediatric PSC-IBD Plus one

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    B Kaj‐Carbaidwala et al. J Pediatr Gastroenterol Nutr. 2025; 80:450–454. Determining the time to cholangiocarcinoma in pediatric‐onset PSC‐IBD

    Background: “Cholangiocarcinoma is a devastating disease, with up to 80% mortality and limited treatment options…A large retrospective cohort study reported that cholangiocarcinoma occurred in 1000 per 100,000 (1%) of children with PSC, with all occurring in children over 15 years of age and at a median of 6 years after the PSC diagnosis…Primary sclerosing cholangitis (PSC) is associated with a 400× increased risk of cholangiocarcinoma.”

    Methods: Review of n = 175 studies resulted in a cohort of n = 21 patients with pediatric‐onset PSC‐IBD‐cholangiocarcinoma

    Key findings:

    • The earliest diagnosis of cholangiocarcinoma was made at 14 years of age.
    • 14% of of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 6 months of the second diagnosis
    • 23% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first year of the second diagnosis
    • 38% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 2 years.
    • 50% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 7 years
    • 50% of patients were between 14 and 25 years old when diagnosed with cholangiocarcinoma

    Based on these data, the authors recommend screening for cholangiocarcinoma in this population of pediatric patients with IBD-PSC. Screening would include ultrasound or magnetic resonance cholangiopancreatography along with serum cancer antigen 19‐9 screening every 6–12 months. At the same time, the authors acknowledge limitations including a highly-selected patient population (selection bias) and relatively small number of patients. The absolute increase in risk for cholangiocarcinoma is not known. This study did not provide an estimate of the number of patients with IBD-PSC who develop cholangiocarcinoma; it only provides data on those with cholangiocarcinoma (thus no denominator to establish risk).

    My take: Children, particularly adolescents, with IBD-PSC are at increased risk for both cholangiocarcinoma and colorectal cancer. The optimal surveillance strategy is still unclear. However, particularly in adolescents, I would favor yearly ultrasound and CA 19-9 for cholangiocarcinoma along with a low threshold for frequent colonoscopy (see ESPGHAN guidelines below).

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    In the news: AP 5/4/25: Cuts have eliminated more than a dozen US government health-tracking programs “U.S. Health Secretary Robert F. Kennedy Jr.’s motto is “ Make America Healthy Again,” but government cuts could make it harder to know if that’s happening…..Among those terminated at the Centers for Disease Control and Prevention were experts tracking abortions, pregnancies, job-related injuries, lead poisonings, sexual violence and youth smoking, the AP found.”

    Anantara Resort, Mai Khao Phuket

    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.

    Infection Risks with Biologic Switches: Findings from Recent Study

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    Briefly noted: AJ Kruger et al. Clinical Gastroenterology and Hepatology 2025. Biologic switch timing and risk of infection in patients with ulcerative colitis/Crohn’s disease: a retrospective study

    Methods: This was a “real-world practice” retrospective study (2017-2022) with 11,992 adult patients who were newly initiating a biologic therapy for UC/CD. 1,293 patients underwent a biologic switch, 64.2% of which were considered an overlapping switch (OS).

    Key findings:

    • Adjusted incidence ratio IR) per 1,000 person years, for any infection, were comparable across switching groups. No significant differences in aHR of infections were found between OS and NOS [any infection aHR: 1.40, P=.17; serious infection aHR: 0.95, P=.93].

    My take (borrowed from authors): “Overlapping switches were common and not associated with an increased risk of serious infection versus non-overlapping biologics.” Thus, shortened washout periods appear to pose minimal safety risks to patients while improving UC/CD therapy management.

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    Bohicket Creek near Charleston, SC

    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..

    ACCURE Trial: Appendectomy As an Adjunct Ulcerative Colitis Treatment Plus One

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    YIZ Acherman, et al. The Lancet Gastroenterology & Hepatology, 2025. DOI: 10.1016/S2468-1253(25)00026-3. Open access! Appendicectomy plus standard medical therapy versus standard medical therapy alone for maintenance of remission in ulcerative colitis (ACCURE): a pragmatic, open-label, international, randomised trial

    Background: “An inverse association between appendicectomy and the development of ulcerative colitis was first reported in 1987, with subsequent case-control studies confirming this observation, and suggesting a possible role of the appendix in ulcerative colitis. In 2016, our research group did a systematic review and meta-analysis of available (case-control) studies. This analysis showed that previous appendicectomy was associated with a significantly reduced risk of developing ulcerative colitis, with an overall odds ratio of 0·39 (95% CI 0·29–0·52).”

    Methods:  Adult patients (n=197) with established ulcerative colitis who were in remission but had been treated for disease relapse within the preceding 12 months were randomly assigned (1:1) to undergo appendicectomy plus continued maintenance medical therapy (intervention group) or to continue maintenance medical therapy alone (control group). Approximately 25% of participants had pancolitis.

    Key findings:

    • The 1-year relapse rate was significantly lower in the appendicectomy group than in the control group (36 [36%] of 99 patients vs 55 [56%] of 98 patients; relative risk 0·65 [p=0·005; adjusted p=0·002). 
    Relapse Rate

    My take (borrowed from the authors): “The ACCURE trial is the first randomised controlled trial evaluating the clinical effectiveness of appendicectomy in maintaining remission in patients with ulcerative colitis without advanced medical therapy (ie, biologicals or small molecules). This trial shows that laparoscopic appendicectomy, in addition to standard medical therapy, significantly reduces the relapse rates within 1 year.”

    Also, NPR notes 5/5/25: NIH cuts baby ‘Safe to Sleep’ team. Here’s what parents should know

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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.

    Understanding the Economic Burden of Inflammatory Bowel Disease

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    J Burisch et al. Clin Gastroenterol Hepatol 2025; 23: 386-395. Open Access! The Cost of Inflammatory Bowel Disease Care: How to Make it Sustainable

    This article is a terrific review of care cost drivers in inflammatory bowel disease (IBD) but it does not actually have useful information on how to make the costs of care sustainable.

    Key points:

    • The most recent data from the United States (U.S.) estimated that the prevalence of IBD
      was 0.7% of the population, representing 2.39 million individuals living with IBD…the annual cost of IBD in the U.S. approximates $50 billion
    • All studies demonstrated a shift over time from costs associated with hospitalizations to costs of medications
    • The costs of prescription drugs for IBD vary significantly worldwide… A particular outlier among high-income countries is the U.S., where manufacturers set prices freely. The lack of
      nationwide price regulation, coupled with the fragmentation of the U.S. health care system and prolonged market exclusivity periods, result in U.S. drug prices that exceed, on average, international prices by several-fold…Even when insurers are successful at negotiating discounts, patients seldom benefit, as costsharing paid at the point-of-sale is based on the full, non-discounted price
    • Using a “top-down” clinical paradigm, guidelines suggest starting biologic medications early to induce remission of moderate-to-severe IBD, thereby reducing risk of complications, surgeries, and hospitalizations and improving quality of life.55,58 A randomized controlled
      trial demonstrated a clear benefit in steroid-free and surgery-free remission among patients randomized to top-down vs step-up care (79% vs 15%; P < .0001) [PROFILE study]

    In terms of improving cost sustainability, here is what the authors propose “Strategies for cost reduction in the clinical treatment of IBD”:

    My take: This article highlights the cost drivers in IBD but does not identify a path that appears to help address affordability.

    This article is one of 11 articles in special issue discussing the future of IBD care.

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    Treatment Disparities in Adult vs. Pediatric IBD Care Related to Provider Specialization

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    JD Lewis et al. Clinical Gastroenterology and Hepatology. 2024; Volume 22, Issue 12, 2475 – 2486.e14. Open Access ! Provider Specialization in Inflammatory Bowel Diseases: Quality of Care and Outcomes

    Methods:  This was a retrospective cohort of newly diagnosed patients with IBD using data from Optum’s deidentified Clinformatics Data Mart Database (2000–2020). The study included 772 children treated by 493 providers and 2864 adults treated by 2076 providers.

    Key findings:

    • In adults, care from an IBD-focused provider was associated with more use of biologics, combination therapy, and imaging and endoscopy, and less mesalamine use for Crohn’s disease (P < .05 for all comparisons)
    • In children, none of the associations between provider focus and process or outcome measures were significant. Although not statistically significant among children, the OR for mesalamine use was 0.64, suggesting a similar association as that seen among adults
    Time to first dispensing of a biologic therapy in (A) children and (B) adults

    My take: This study indicates significant treatment disparities between IBD-focused care providers and providers without an IBD focus in the care for adults, but not in the care of children. This could be related to improved collaboration among pediatric care providers, better training, and parental involvement.

    In addition, this study focused on patients with newly-diagnosed disease. Treatment is more complicated in patients who have not responded to initial treatments; as such, IBD-focused providers may be more important in this population.

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    Comparing Infliximab, Adalimumab, and Vedolizumab in Adults and Children with Ulcerative Colitis

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    O Atia et al. Infammatory Bowel Diseases, 2025, 31, 617–624. Durability of the First Biologic in Children and Adults With Ulcerative Colitis: A Nationwide Study from the epi-IIRN

    This was a nationwide Israeli study with 15,111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years. The dataset includes ~98% of the Israeli population; “the accuracy of medication data is high, as the Israeli health care system provides medications almost free of charge through the HMOs, and the electronic dispensing of drugs contributes to reliable and precise data.”

    Key findings:

    • After 5 years of treatment, 43% of the patients with UC sustained their first biologic
    • The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively)
    • Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively) or combotherapy (78%/56% vs 91%/58%, respectively)
    • Durability of infliximab at 1 yr and 5 yrs was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; , P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%)
    • The durability rate was similar for vedolizumab monotherapy at 1 yr and 5 yrs (77%/56%) compared with adalimumab monotherapy (69%/52%), and infliximab monotherapy (73%/55% vs 62%/44%). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%), respectively;

    My take: When looking at the durability plots, the three main biologics in this study, infliximab, adalimumab and vedolizumab, performed similarly. Whether therapeutic drug monitoring would influence theses results is not clear. It is interesting that a recent study in the pediatric population found that combination therapy was important for adalimumab and not infliximab (see: Why Do Children Taking Adalimumab Benefit from Methotrexate Dual Therapy?)

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    Also, from AGA Today (3/20/25): FDA Approves Guselkumab To Treat Patients With Crohn’s Disease

    HCPlive (3/20, Campbell) reports the FDA on Thursday announced the approval of “guselkumab (Tremfya) for the treatment of adults with moderately to severely active Crohn disease.” The announcement from Johnson and Johnson claims the “approval is based on data from multiple phase 3 trials, including the GALAXI trials, which found guselkumab outperformed ustekinumab (Stelara) for multiple endoscopic endpoints. The agent now boasts indications for moderately to severely active Crohn disease and moderately to severely active ulcerative colitis (UC).” This is the fourth indication for guselkumab in the US

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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.