Category Archives: inflammatory bowel disease

Treating Pediatric Metastatic Crohn’s Disease

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E Chang et al. JPGN Reports. 2025;1–8. DOI: 10.1002/jpr3.70022. Open Access! Genital Crohn’s disease in pediatrics and genetic associations

This case report of four patients provides a good review of metastatic Crohn’s disease (MCD). MCD indicates that there is noncontiguous dermatological spread of CD involving the genitalia and perineum.

Key points:

  • “Less than 100 cases of pediatric MCD have been reported in the literature to date. These lesions are characterized by swelling, plaques, nodules, fissures, ulcerations, or crusts. In children, MCD typically presents as genital swelling with or without erythema in approximately 85% of cases.”
  • “Prior studies have shown that MCD co-occurs with CD in 50.8% of children, while others may develop GI symptoms after MCD diagnosis (15.3%) or even lack signs of CD (11.9%).”
  • “Scrotal histopathology revealed granulomatous inflammation, and genetic testing identified pathogenic variants in NOD2, COL7A1, and Chek2, as well as additional variants of uncertain significance.”
  • The optimal treatment is not clear. “Prior case reports and case series have shown positive responses to TNF-α inhibitors, but relapses may be common. Similarly, only partial improvement was noted in our patients treated with infliximab and adalimumab.”

Discussion: “Many patients do not demonstrate GI symptoms and may experience significant delays in diagnosis.”

My take: This article provides a good review of metastatic Crohn’s disease which is a rare problem. I have had two patients with this disorder. This problem fits the adage of “the more you see, the more you know; and, the more you know, the more you see.”

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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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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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Do Setons Improve Outcomes in Anti-TNF Treatment for Fistulas?

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J McCurdy et al. AP&T 2025; https://doi.org/10.1111/apt.70081. The Impact of Setons on Perianal Fistula Outcomes in Patients With Crohn’s Disease Treated With Anti-TNF Therapy: A Multicentre Study

This study included 221 patients — 81 with setons and 140 without setons. Patients were treated with their first anti-TNF therapy for perianal fistulizing Crohn’s disease (PFCD) after undergoing a pelvic MRI between 2005 and 2022 from 6 North American centers. Our primary outcome was major adverse fistula outcome (MAFO), a composite of repeat local surgical intervention, hospitalization, or fecal diversion for PFCD.

Key findings:

  • Patients with setons had similar rates of MAFO (HR 1.23; 95% CI, 0.68–2.21) and fistula remission at 6 months (OR, 0.81; 95% CI, 0.41–1.59) and 12 months (OR, 0.63; 95% CI, 0.31–1.27) compared to patients without setons
  • In patients with abscesses, there were lower rates of MAFO (HR, 0.49; 95% CI, 0.19–1.25) but not statistically significant in patients with setons

My take: This study indicates that seton placement may not be needed in patients who are starting anti-TNF therapy with fistulizing disease, especially if there is not an abscess present.

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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.

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.

Dr. Maria Oliva-Hemker: Positioning Therapies for Pediatric Crohn’s Disease

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Recently, Dr. Maria Oliva-Hemker gave our group an excellent update on Crohn’s disease therapies.  My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides.

Key points:

  • Early advanced therapy results in better outcomes (see The PROFILE study results below as one example)
  • Anti-TNFs are the only therapy with a specific FDA pediatric indication. Medications can take 8-10 years after use in adults for pediatric labeling
  • IL-23 specific agents (like risankizumab) are more effective than ustekinumab that target both IL-23/IL-12
  • Recent studies show that ustekinumab is effective in children. Also, in patients who respond to ustekinumab, there is good durability
  • Infliximab is a top-line therapy in Crohn’s disease
  • Risankizumab is a top-line therapy in both biologic-naive and biologic-exposed patients with Crohn’s disease. Higher maintenance doses may capture more patients.
  • Upadacitinib is a very good therapy in patients with prior advanced therapies with either Crohn’s or ulcerative colitis. It also has a rapid onset of action (within 2 weeks)
  • Vedolizumab is less effective in those who are biologic-exposed. However, patients with predominantly colonic (UC-like) involvement may be better-suited for this therapy
  • Close monitoring and treat-to-target approaches are recommended. Usually followup scope is undertaken after one year (&/or one year after switching therapy)
  • Combination advanced therapies have shown effectiveness but it is unclear which combinations are optimal
This slide shows the Montreal Classification, an organ-based phenotype, to describe the anatomic extent and behaviors of Crohn’s disease;. The figure on the right illustrates extraintestinal manifestations of IBD. It is expected that disease classification will rely more on a molecular based approach.
The STRIDE project which defined goals of treatment was the result of consensus achieved by the International Organization of IBD. The first recommendations came out in 2015 and then these were updated in 2021 to incorporate a pediatric component.
The PROFILE study with 386 adults showed how important early effective advanced therapies. Patients receiving infliximab/azathioprine within a median of 15 days from diagnosis had remarkably better outcomes compared to step up treatment with prednisone + azathioprine.
The cytokine IL12 and IL23 shown as circles with 2 subunits attaching to their receptors share a p40 subunit (shown in red). Ustekinumab binds to that p40 subunit thereby inhibiting both the IL12 and IL23 pathways. IL23 inhibitor. Risankizumab, Mirkizumab, Guselkumab inhibit only the p19 subunit (shown in blue) and so  they only downregulate the IL-23 pathway.
Jak inhibitors targets are intracellular in location.
Pediatric data: Multicenter 2015-2020; primary outcome was CS-free remission after 1 yr. Prior to use, 50% failed 1 anti TNF and 30% 2 anti TNF. At one year, 59/101 were in steroid free remission
Upadactinib studies: Oral induction dose for UC and CD is 45 mg daily for induction
and with reduction in maintenance to 30 mg or 15 mg
Due to limited head-to-head studies, network meta analyses provides indirect evidence of comparative effectiveness. It relies on how effective a medication was compared to placebo. One of the problems with these comparisons is that there are different populations in each of these studies.
In patients who need speed to reduce symptoms, upadacitinib is favored over IL-23 agents

Though Dr. Oliva-Hemker’s lecture did not focus on ulcerative colitis, she did note that their center has recommended frequent colonoscopies (often yearly) in many of their patients with the combination of ulcerative colitis and PSC. This is due cases of colon cancer in their pediatric cohort.

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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.

Antibiotics and IBD Risk: A Systematic Review

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R Duan et al. Clin Gastroenterol Hepatol 2025; 23: 45-58. Open Access! Antibiotic Exposure and Risk of New-Onset Inflammatory Bowel Disease: A Systematic Review and Dose-Response Meta-Analysis

Twenty-eight studies involving 153,027 patients with IBD were included.

Key findings:

  • Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29–1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08–1.68). ‘
  • This association existed for both Crohn’s disease and ulcerative colitis, as well as in children and adults for prescription-based studies. 

Some of the limitations:

  1. There was statistical heterogeneity was high in the primary analysis, possibly because of inconsistencies in study design
  2. Most studies included a clear lag time, yet an inadequate lag time still creates the possibility of reverse causality.
  3. The authors could not disentangle the risk of antibiotics from the risk of infection in leading to the development of IBD.
Nonlinear dose-response relationship between antibiotic exposure and risk of new-onset IBD (solid black line and short dash black line represent estimated ORs and corresponding 95% CIs of nonlinear relationship)

My take: This is another study showing an association between antibiotic use and new-onset IBD. While this study does not prove causation, it is another reason for good antibiotic stewardship.

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Managing Drug-Induced Acne in IBD: A Guide for Gastroenterologists

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MJ Temido et al. Am J Gastroenterol 2025;120:125–134. Drug-Induced Acne in Inflammatory Bowel Disease: A Practical Guide for the Gastroenterologist

“Corticosteroids and Janus kinase inhibitors (JAKi) are commonly used for the treatment of inflammatory bowel disease (IBD) and are known to aggravate a prior tendency to acne or trigger the development of new acneiform eruptions. Both randomized controlled trials and real-world studies have identified acne as one of the most common treatment-emergent adverse events in JAKi… This review examines the characteristics of drug-induced acne in IBD treatments, provides a practical guide for gastroenterologists to manage mild-to-moderate occurrences, and highlights when to seek specialist dermatology advice.”

My take: This is a helpful review of acne management in the setting of IBD.

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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.

IBD Briefs: Upadacitinib in Children, Predicting Crohn’s Disease, and Autoimmune Diseases Associated with IBD

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J Runde et al. J Pediatr Gastroenterol Nutr. 2025;80:133–140. Upadacitinib is associated with clinical response and steroid-free remission for children and adolescents with inflammatory bowel disease

In this single-center retrospective study, n=20 (3 CD, 13 UC, 4 IBD-U), steroid-free clinical remission (SF-CR) was seen in 75% (16/20) following induction and maintained in 65% (11/17) reaching Week 24 of therapy

J Gaifem et al. Nature Immunology 2024; 25: 1692-1703. Open Access! A unique serum IgG glycosylation signature predicts development of Crohn’s disease and is associated with pathogenic antibodies to mannose glycan.

“Analysis of preclinical serum samples, up to 6 years before IBD diagnosis (from the PREDICTS cohort), revealed the identification of a unique glycosylation signature on circulating antibodies (IgGs)…[which] elicits a proinflammatory immune pathway through the activation and reprogramming of innate immune cells.”

LR Jolving et al. Inflamm Bowel Dis 2025; 31: 87-94. Children and Adolescents Diagnosed With Inflammatory Bowel Disease Are at Increased Risk of Developing Diseases With a Possible Autoimmune Pathogenesis

Using Danish registry and 50-fold matched controls, there was a significant increase for a large number of autoimmune diseases: The adjusted hazard ratio after full follow-up was 4.72 for psoriatic arthritis, 5.21 for spondyloarthritis, 2.77 for celiac disease, 2.15 for rheumatoid arthritis, 1.69 and 1.64 for type 1 and type 2 diabetes, respectively. For thyroid disease, it was 1.16.

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