Tag Archives: Crohn’s disease

Infliximab Biosimilars As Effective as Remicade In Children With Inflammatory Bowel Disease

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RM Maltz, J Adler. J Pediatr Gastroenterol Nutr. 2026; 83: 710-716. ImproveCareNow Pediatric IBD Learning Health System. Infliximab originator and biosimilars have similar efficacy in children with inflammatory bowel disease.

Background: “Biosimilars are nearly identical to the originator biologic with only minor differences, usually in the inactive components such as buffers or stabilizers, which have no effect on efficacy as shown in adult studies and limited pediatric studies13–22…The introduction of biosimilars has significantly contributed to competition, which has driven down the price of the infliximab originator along with infliximab biosimilars.23 The price of the infliximab originator dropped by more than 50% between 2018 and 2021.23“

Methods: This was a retrospective cohort study evaluating prospectively collected data from the ImproveCareNow (ICN) Network registry. 428 children were studied using propensity score matching.

Key findings:

  • Efficacy at 12 months was similar as assessed by steroid-free clinical remission (p = 0.25), height-z-score (p = 0.68), hematocrit (p = 0.37), albumin (p = 0.40), and erythrocyte sedimentation rate (p = 0.06). 
  • Time to infliximab discontinuation (p = 0.21), time to surgery (p = 0.79), and time to hospitalization (p = 0.66) were comparable between infliximab originator and biosimilar users
  • In subset of patients with available results (fewer than one in three patients had calprotectin results available), fecal calprotectin values were statistically higher (p = 0.032) at 12 months in patients in the biosimilar cohort. At baseline, fecal calprotectin values were >250 in 11 (60%) of biosimilar cohort compared to 22 (38%) of the originator cohort. At 12 months, 36 (54%) in the biosimilar cohort and 28 (49%) in the originator cohort had fecal calprotectin values >250.
Outcomes comparing the infliximab originator (blue dashed line) to infliximab biosimilar (red solid line). Time to discontinuation of originator or biosimilar infliximab with 95% confidence intervals
Outcomes comparing the infliximab originator (blue dashed line) to infliximab biosimilar (red solid line). Proportion needing intestinal surgery with 95% confidence intervals
Outcomes comparing the infliximab originator (blue dashed line) to infliximab biosimilar (red solid line). Proportion needing hospitalization with 95% confidence intervals

My take (borrowed in part from the authors): “This study adds to the growing literature that children with IBD, regardless of initiating infliximab originator or a biosimilar, have similar clinical outcomes at 1 year.16–19, 21” Despite this, many families still request/prefer Remicade.

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Pre-Crohn’s Disease Stool Promotes Colitis in Germ-Free Mice Plus One

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C Dang et al. Gastroenterology, 2026; 171, 489-503. Pre-Crohn’s Disease Stool From Discordant Siblings Promotes the Development of Colitis in Germ-Free Mice

Methods: This study was conducted as part of The GEM Project, a prospective cohort study of healthy first-degree relatives of CD patients. Germ-free mice were colonized with fecal samples from 12 pairs of discordant siblings, where one sibling later developed CD (pre-CD), and the other remained a healthy matched control (HMC). The microbiome collected wa ~2.6 years before CD diagnosis.

Key findings:

  • Mice receiving pre-CD stool exhibited increased weight loss, fecal lipocalin-2, and intestinal histologic damage compared with mice receiving HMC stool. Thus, mice colonized with stool from individuals who later developed Crohn’s disease showed significantly faster and more severe intestinal inflammation compared with mice colonized with stool from the siblings who remained healthy.
  • Fecal metabolomic analysis revealed differences in 40 metabolites between pre-CD and HMC colonized mice.

My take:

  1. Silly take: It’s a good idea not to eat someone else’s poop — it might make you sick!
  2. Serious take (borrowed in part from the authors): “The stool microbiome of individuals susceptible to CD is altered years before diagnosis, exhibiting greater inflammatory potential when transferred to susceptible mice.” These studies about the microbiome are remniscent of studies 15-20 years ago indicating that manipulation of the microbiome may play a role in the developement of obesity and Kwashiokor. (Related posts: Could antibiotics make you fat? gutsandgrowth, Microbiome and the risk of Kwashiokor | gutsandgrowth, Microbial transfer for metabolic syndrome? | gutsandgrowth)

Related article: M Xue, C McShane, J Kim et al. Gastroenterol 2026; 171: 641-655. Open access! β-Glucan and Inulin Estimated Intake Are Associated With Reduced Risk of Crohn’s Disease, Improved Gut Barrier and Systemic Inflammation Markers, and Multi-Omic Signatures in a High-Risk Cohort

Methods: The Genetic, Environmental, Microbial (GEM) Project prospectively followed asymptomatic first-degree relatives of individuals with CD. Habitual intake of total fiber and select fiber subtypes was estimated from baseline food frequency questionnaires and biologic samples were collected.

Key findings:

  • During a median follow-up of 8.5 years of 3314 first-degree relatives, 94 developed CD. Higher β-glucan (HR, 0.70) and inulin (HR, 0.68 intake were associated with lower CD risk.
  • Higher β-glucan and inulin intake were associated with lower lactulose–mannitol ratio, lower abundance of pathobionts (Ruminococcus torques and Lachnoclostridium), and lower concentrations of inflammation- and barrier-related proteins.
  • Increased β-glucan found in oats, barley and grains. Increased inulin found in garlic, onions, leeks and asparagus

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Real-World Outcomes of Risankizumab in Children With Crohn’s Disease

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Briefly noted:

EA Spencer et al. Journal of Crohn’s and Colitis. 2026; 20: jjag134. https://doi.org/10.1093/ecco-jcc/jjag134 Real-world effectiveness and safety of risankizumab induction and maintenance therapy in pediatric patients with Crohn’s disease: a multicenter retrospective analysis.

Methods: This was a retrospective, global multicenter cohort of patients <18 years initiating risankizumab monotherapy (2022-2025). Among the 96 study participants, 38% had prior ustekinumab exposure.

Key findings:

  • Post-induction corticosteroid-free clinical remission (CFR) was achieved in 28/68 (41%), clinical response in 37/68 (54%), and combined CFR + CRP remission in 22/68 (32%).
  • Week 30 and 54 CFR were attained in 34/68 (50%) and 34/68 (50%), respectively.
  • No serious safety events occurred.

My take: This study bolsters previous studies showing that risankizumab is an effective treatment for Crohn’s disease in the pediatric age group.

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AFFIRM Study: Subcutaneous Induction-Maintenance Data for Risankizumab

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Charlie Lees is a Professor of Gastroenterology, University of Edinburgh.

From Charlie Lees on X (10/14/26):

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AI for Capsule Endoscopy:

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D Fan et al. Clin Gastroenterol Hepatol 2026; 24: 2571-2583. Open Access! INTELCAPE: A Deep Learning-Powered System for Automated, High-Accuracy Crohn’s Disease Diagnosis via Capsule Endoscopy

Methods: In this retrospective, multi-center study with data from 2 Chinese hospitals, the authors developed artificial intelligence, INTELCAPE, for a multi-task deep learning system, to perform small-intestine segmentation, lesion detection, and CD diagnosis from full (capsule endoscopy) CE videos.

Key findings:

  • “INTELCAPE achieved state-of-the-art performance across all tasks.”
  • “For lesion detection, it achieved area under the curve values of 0.993 (Cohort 1) and 0.980 (Cohort 2), with 99.33% classification accuracy, which was comparable to that of specialists (97.83%) but superior to that of residents (91.05%; P < .001).”
  • “For CD diagnosis, INTELCAPE demonstrated robust generalizability, achieving area under the curve values of 0.982 (Cohort 1) and 0.984 (Cohort 2) with 90% diagnostic accuracy, comparable to that of specialists (93.33%) but 10-fold faster (P < .001).”
  • “INTELCAPE improved doctors’ diagnostic accuracy (76.7%–94.8%; P < .001), while reducing their interpretation time (67.9–22.5 minutes; P < .001).”

Discussion Points:

  • “CE generates thousands of images per examination, imposing a substantial analytical burden on clinicians. Manual analysis is labor-intensive and prone to human error, increasing the risk of missed lesions, particularly those with subtle appearances.”
  • “Real-world clinical workflows will require prospective validation on “all-comers” populations, robust handling of poor-quality videos, and device-specific fine-tuning.”

My take: Capsule endoscopy appears to be an ideal target for AI assistance. It has the potential to improve accuracy, reduce time, and augment the performance of less experienced clinicians.

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The Tricky Problem of IBD with IBS-like symptoms

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Ma C, Ford A, Hashash J et al. Gastroenterology, 2026; 171, 504-520. Open Access! Recommendations for the Evaluation and Management of Inflammatory Bowel Disease With Irritable Bowel Syndrome–Like Symptoms: A Joint Rome Foundation and International Organization for the Study of IBD (IOIBD) Consensus

Background:

  • “A substantial proportion of persons with inflammatory bowel disease (IBD) in remission continue to experience abdominal pain, altered bowel habits, and bloating that resemble irritable bowel syndrome (IBS). Lack of standardized definitions and evidence-based management strategies leads to diagnostic ambiguity and potentially unnecessary escalation of IBD therapy. A joint Rome Foundation/International Organization for the Study of Inflammatory Bowel Disease Working Team developed consensus recommendations on nomenclature, evaluation, and treatment of IBD with IBS-like symptoms.”
  • “A meta-analysis of 27 studies demonstrated that 1 in 3 individuals with IBD reported
    coexisting IBS, although estimates were heterogeneous and few studies objectively excluded active disease (11.2% to 63.6%).[1] Among those with endoscopic or histologic
    remission, 1 in 4 reported IBS-like symptoms.”

Methods: A multidisciplinary international panel applied a modified RAND/UCLA Appropriateness Method and determined recommendations for evaluation and management of these patients.

Terminology:

  • “The preferred term was “IBD with IBS-like symptoms,” defined as abdominal pain, bowel habit change, and/or bloating not explained by active inflammation or structural disease.”

Pathophysiology:

Evaluation to determine whether GI symptoms are related to IBD or are related to IBS-like symptoms

Key points:

  • “An FC [fecal calprotectin] below 150 μg/g is considered normal, but persons with IBD with ongoing symptoms may require endoscopic evaluation even with a normal FC, especially in the setting of small bowel involvement or after surgery in CD.”
  • “In clinical care, the diagnosis of IBD with IBS-like symptoms can be supported using the Rome Clinical Diagnostic Criteria (having symptoms sufficiently bothersome to seek health care for at least the prior 8 weeks or when other conditions have been excluded).”
  • Dietary treatments of IBS symptoms were recommended including psyllium and a trial of a low FODMAP diet.
  • Medication treatments of IBS symptoms were recommended including TCAs, SSRIs, SNRIs, antidiarrheals (e.g. loperamide), antispasmotics, peppermint oil, osmotic laxatives, 5-HT4 receptor agonists and secretagogues (e.g. linaclotide).
  • Behavior therapies including GI-focused cognitive behavioral therapy and gut-directed hypnotherapy were recommended
Treatment algorithm

My take: Overall, this expert panel endorsed a broad-range of current IBS treatments for patients with well-controlled IBD experiencing ongoing GI distress. This paper focuses attention to this difficult clinical problem in which many patients, historically, have received escalating IBD therapy rather than IBS therapies. Part of the problem is that it is difficult to be certain that a patient’s IBD is well-controlled and that there are no structural problems (e.g. strictures). In addition, many patients have very mild findings and it can be hard to know if these findings are enough to account for the symptoms. The opposite problem can also occur in which patients have very active IBD yet have few clinical complaints.

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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.

Elegant Study: Childhood Exposure to a Sibling with Crohn’s Disease and Disease Susceptibility

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R Chen et al. Gut. Epub ahead of print, August 31, 2026. doi:10.1136/
gutjnl-2026-339257. Childhood exposure to a sibling with Crohn’s disease alters gut microbiome and Crohn’s disease susceptibility

Thanks to Mike Hart for sharing this reference. This study is worth reading in its entirety due to the combination of experiments. This is a fairly long post to summarize the most important findings.

Background:

“In a study of 2756 Dutch families, gut microbiome composition and function were more alike between siblings than between parent-offspring pairs or spouses…These findings suggest that increased disease susceptibility among siblings of individuals with CD may be mediated by their shared gut microbiome.”

Methods:

  1. The authors used the prospective Genetic Environmental Microbial (GEM) Project and the nationwide South Korean database to assess the association between childhood exposure to affected siblings and CD onset (n=3126). This was validated in the South Korean dataset.
  2. A T-cell transfer model of colitis in germ-free mice was conducted to investigate the effects of stool from childhood-exposed (n=4) versus adult-exposed (n=4) siblings.
  3. An integrative risk model combining faecal calprotectin (FCP) and microbial enterotypes was trained and internally validated within the GEM cohort.

Key findings:

  • “In the GEM cohort, childhood exposure to an affected sibling was associated with a fourfold higher risk of developing CD compared with adult exposure (adjusted HR (aHR) 4.00; p=5.3×10−4), which was validated in the South Korean dataset (aHR 2.54; p=6.0×10−6).”
  • “Childhood exposure was associated with reduced abundances of Lachnospira,
    Roseburia     and Colidextribacter, reductions that mediation analysis identified as partially mediating CD risk.”
  • “In vivo, transplantation of childhood exposure-associated microbiota into germ-free recipient mice exacerbated colitis and elevated mucosal interleukin-22 expression, supporting a potential mechanistic role.”
  • This “model identified siblings with elevated FCP and Blautia-enriched or
    Prevotella-enriched enterotypes as highest risk, with a 10-year cumulative incidence of 22.5%.”
Figure 1b. Childhood exposure to CD was demonstrated to associate with increased disease susceptibility in the GEM cohort, and confirmed in an independent nationwide dataset.
Figure 1d. Among siblings with childhood exposure to CD, the authors developed and validated a risk stratification based on gut inflammation and enterotypes to identify individuals at high risk of CD onset
Figure 3a. Bar chart presenting the proportion of individuals with gut barrier dysfunction and gut inflammation among those exposed to CD during childhood (blue) or adulthood (orange).
Figure 5d. Kaplan-Meier curves showing the cumulative CD-free probability for individuals classified as having non-inflammation (blue), gut inflammation with Bact2 (green) and gut inflammation with Blau/Prev (orange) in the GEM cohort.

Discussion

  • This “study demonstrates that the timing of exposure to a sibling with CD, specifically childhood versus adult exposure, plays a critical role in disease susceptibility. Childhood exposure was associated with a fourfold higher risk of CD, potentially mediated by alterations in the gut microbiome.”
  • “Genetic predisposition has traditionally been considered the primary explanation for the elevated disease risk among siblings of persons with CD. However, genetic factors account for only about 10% of the variance in CD risk…childhood exposure to a sibling
    with CD, compared with adulthood exposure, was associated with a fourfold increased risk of disease onset, independent of the CD-PRS [CD – polygenic risk score].”
  • This study adds to “a growing body of evidence [that] implicates early-life exposures in CD pathogenesis. A recent meta-analysis reported that prenatal exposure to antibiotics and cigarette smoking increased the risk of CD, while breastfeeding was protective. Similarly, a large population-based study found that rural residence during childhood, but not adulthood, was associated with a lower risk of CD.”

Limitations:

  • Participants were from high-income countries.
  • Study did not include dietary intake.
  • These findings do not prove causation. There may be additional unrecognized genetic factors between the groups with exposure before and after 18 years of age.

My take: The increasing prevalence of Crohn’s disease, particularly over the last few decades, must be related to environmental factors; population genetics and genetic predisposition are unlikely to rapidly change. This is a very important study supporting the notion that exposure to siblings with Crohn’s disease and alteration of the gut microbiome increases the risk of Crohn’s disease. By identifying a microbiome group with a higher risk, this study may facilitate research to determine whether manipulation of the gut microbiome could reduce the likelihood of developing Crohn’s disease. If we can reduce Crohn’s disease in a high risk population, it may allow broader use of the same treatment principles to lower risk groups as well.

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The Safety and Effectiveness of Early Anti-tumor-necrosis-factor Therapy for Penetrating Crohn’s Disease in Pediatrics

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BD Constant et al. American Journal of Gastroenterology Publish Ahead of Print, July 1, 2026. | DOI: 10.14309/ajg.0000000000004104. The Safety and Effectiveness of Early Anti-tumor-necrosis-factor Therapy for Penetrating Crohn’s Disease Complications in Children

Methods: This was a multicenter retrospective study examining the safety of anti-TNF therapy in children (n=203) with Crohn’s disease (CD) who developed internally penetrating complications (IPCs; abscesses and inflammatory masses). The exposure timeframe was anti-TNF administration within 30 days of IPC diagnosis.

Key findings:

  • In Cox analyses, early anti-TNF was not linked to infectious serious adverse events (iSAE), noninfectious CD-related SAE, or surgeries, but was associated with increased combined clinical-biochemical-corticosteroid-free remission (hazard ratio 1.65).
  • Surgical risk differed by percutaneous drainage (PD) status: patients receiving early anti-TNF and PD had lower risk versus PD alone (event-free survival 58% vs 15%, log-rank P = 0.04).

My take: For many years, my practice has been to use early anti-TNF even in patients with internally penetrating complications. This study confirms that anti-TNF therapy may be beneficial in this setting.

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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

Severe Consequences of Pediatric Perianal Crohn’s Disease

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A Strom et al. Clin Gastroenterol Hepatol 2026; 24: 1960-1969. Perianal Disease in Pediatric-Onset Crohn’s Disease: Incidence, Disease Course, and Long-Term Outcomes

Methods: In this nationwide Danish registry, a pediatric-onset CD cohort from 1980 to 2022 was identified. Outcomes for patients with and without perianal disease were examined.

Key findings:

  • There were 2356 patients with pediatric-onset CD, of whom 769 (32.6%) developed perianal CD. The cumulative incidence of perianal CD was 14.0%, 21.1%, and 28.1% after 1, 5, and 10 years.  After 30 years, the incidence rate was 45.2%.
  • A stoma was required in 308 (40.1%) and 147 (9.3%) patients with and without perianal disease, respectively (aHR, 2.8).
Probability of Major Abdominal Surgery in Patients with and without Perianal Disease
  • When comparing patients with/without perianal disease, the aHR for major abdominal surgery, cancer, and mortality were 1.5, 0.8, and 1.5 , respectively.
Probability of Mortality in Patients with and without Perianal Disease
  • When comparing patients with/without perianal disease, the aHR for mortality was 1.5. Of mortalities, 35 had perianal disease (4.6%; mortality rate, 2.2/1000 person-years) and 33 did not (2.1%; mortality rate, 1.4/1000 person-years). However, the confidence interval was 0.9-2.7) indicating the precision of this finding is low.

Discussion: “In our study, patients without perianal disease were diagnosed with CD more frequently in recent decades than patients with perianal disease. The differences in distribution of CD diagnosis over calendar years may be due to shorter follow-up among patients diagnosed with CD in recent decades, improved treatment delaying disease progression, and increased detection of milder CD phenotypes over time.”

My take: This study reinforces and quantitates the view that having perianal Crohn’s disease portends an increased risk for severe complications. With improving treatments, perhaps the outcomes will be more favorable now and in decades hence.

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Discordant Clostridiodes difficile Testing In Patients with Inflammatory Bowel Disease

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P Ramakrishan et al. Inflamm Bowel Dis 2026; 32: 1313–1320. Discordant Clostridioides difficile testing as a predictor of inflammatory bowel disease therapy escalation

Background: “In the general population, individuals with discordant tests (PCR+/TOX−) have similar outcomes to PCR− individuals, suggesting that this group represents individuals colonized with C. difficile.[14]”

Methods: In this retrospective study (n=117), outcomes assessed included CDI-directed therapy or escalation of IBD treatment.

Key findings:

  • 79% (93/117) were PCR+/TOX− and 21% (24/117) were PCR+/TOX+
  • PCR+/TOX+ patients had significantly higher CRP (98 vs 6 mg/L, P = .005)
  • PCR+/TOX− patients had more severe underlying IBD and higher rates of steroid use (48% vs 21%, P = .02) and were significantly more likely to require IBD therapy escalation (54% vs 25%, P = .004). Multivariable analysis showed PCR+/TOX− status (odds ratio [OR], 3.2) was a significant predictor of IBD treatment escalation. Antibiotic use did not significantly alter the need for escalation among PCR+/TOX−  patients.

Discussion:

  • “Most IBD patients who are PCR+/TOX−  are colonized with C. difficile, and IBD treatment could be considered rather than delaying for CDI therapy.”

My take: In patients with IBD, PCR-positivity for C diff is frequently a false positive due to high rates of colonization in this population. Patients who have their infection confirmed with an immunoassay are much more likely to respond to C diff therapy.

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Resources:

National Civil Rights Museum in Atlanta, GA. One of the powerful exhibits is a Woolworth lunch counter replica with headphones.  With your eyes closed, the exhibit challenges you to keep your hands on the counter as one receives menacing threats like ‘Boy, I’m going to kill you.’