Category Archives: inflammatory bowel disease

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.’ 

Impact of 5‐Aminosalicylic Acid Discontinuation in Children with Ulcerative Colitis Receiving Biologic Therapy

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G D’Arcangelo et al. J Pediatr Gastroenterol Nutr 2026; 83: 96-107. Open Access! Impact of 5-Aminosalicylic acid discontinuation in children with ulcerative colitis on biologic therapy: A propensity score-matched study

Background: Several adult-based studies have found that discontinuing 5-ASA at the initiation of anti-TNF therapy is not associated with worse clinical outcomes. “Ungaro et al. analyzed data from over 3500 patients in the United States and Denmark and found no increased risk of adverse outcomes following mesalamine discontinuation after the initiation of anti-TNF therapy.18 Based on this evidence, the American Gastroenterological Association recommends discontinuing mesalamine in patients with moderate-to-severe UC who are starting biologics or small molecules and achieve remission.19 However, this recommendation is based on low-quality evidence, and pediatric guidelines do not offer a similar directive.2“

Methods: Retrospective, multicenter, case–control study which included 227 pediatric patients in the final analysis after matching (85 [37.5%] cases and 142 [62.5%] controls].

Key findings:

  • Children who discontinued 5-ASA were at higher risk of courses of steroids (Log-Rank p = 0.003) and hospitalization (p = 0.08). This finding persisted with multivariate Cox regression analysis.
  • “Fixed timepoint analyses showed a statistically significant increase in the odds of adverse outcomes at the 6-month follow-up (including hospitalizations and acute severe colitis), with no significant differences detected at 12, 18, or 24 months, and only a non-significant trend toward higher hospitalization risk over time.”

My take: This is an intriguing study with a small sample size of pediatric IBD patients. Given the findings in adults, it is customary to stop 5-ASA at the time of initiation of biologic therapy. However, this study indicates that pediatric patients—who often present with more extensive and severe disease—may have some benefit from overlapping these therapies, especially during the first six months. A prospective pediatric study would be helpful.

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

Does Isolated Ulcerative Proctitis Increase the Risk of Rectal Cancer?

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AH Everhov et al. Gastroenterol 2026; 171: 158-160. Open Access! Incidence of Rectal Cancer in Patients With Isolated Ulcerative Proctitis: A Population-Based Cohort Study

Methods: Using a prospective nationwide registry (SWIBREG) (1997-2023), there were 15,957 individuals diagnosed with isolated proctitis and matched to 158,079 population comparators. Median followup for patients with isolated proctitis was 10.8 years.

Key findings:

  • Rectal cancer incidence was 0.11% in patients and 0.09% in comparators at 5 years and 0.16% and 0.21%, at 10 years.
  • During follow-up, inflammation remained limited to the rectum in 60% of patients, whereas 23% developed left-sided colitis and 17% developed extensive colitis

Discussion Points:

  • “Results from this nationwide study indicate patients with isolated proctitis have no elevated rectal cancer risk with respect to the general population.”
  • “40% of patients experienced disease extension” which is similar to prior studies.
  • “European (European Crohn’s and Colitis Organisation)9 and US (American College of Gastroenterology)10 guidelines endorse standard population screening in limited-extent disease, and our data support these recommendations.”

My take: This should provide a lot of reassurance for our patients with isolated proctitis.

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Interleukin-10 Autoantibodies and Development of IBD Plus One

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N Gharahdaghi et al. N Engl J Med 2026;394: 2212-2222. Interleukin-10 Autoantibodies and HLA-DRB1*01:03 in Inflammatory Bowel Disease

Background: “The allele HLA-DRB1*01:03 is the strongest genetic risk factor not only for susceptibility to ulcerative colitis but also for complicated phenotypes, including acute severe ulcerative colitis and an increased likelihood of surgical resection.2-5 However, the underlying pathogenic mechanism linking this HLA allele to disease remains unclear.”

“Neutralizing autoantibodies against interleukin-10 can result in a phenocopy of monogenic defects of interleukin-10 signaling in children and may be associated with inflammatory bowel disease (IBD)…In one child, anti–interleukin-10 titers and disease activity responded to B-cell–depleting anti-CD20 therapy.12“

Methods:

Key findings:

  • Interleukin-10–neutralizing autoantibodies were detected in 173 of 4909 patients with IBD (3.5%) and in none of 1006 controls (P<0.001)
  • High anti–interleukin-10 activity in serum was associated with a reduction in detectable interleukin-10 and with an exaggerated proinflammatory cytokine response
  • Anti–interleukin-10 seropositivity was strongly associated with HLA-DRB1*01:03 on the basis of imputed data from the Oxford cohort (odds ratio, 50.0), the U.K. IBD BioResource cohort (odds ratio, 24.7), and in a high-resolution sequencing analysis of data from the Oxford cohort (odds ratio, 29.5)

Discussion Points:

  • “The genetic association between HLA-DRB1*01:03 and anti–interleukin-10 autoreactivity provides mechanistic insight into one of the strongest known genetic susceptibility factors for IBD, with possible diagnostic, prognostic, and therapeutic implications.”
  • “Monogenic interleukin-10–signaling defects tend to manifest during infancy with colonic and penetrating disease, poor response to IBD therapies, high inflammatory activity with notably elevated C-reactive protein levels, and a high incidence of postoperative complications.27 It will be informative to establish the extent to which anti–interleukin-10 seropositivity associates with a similar disease pattern.”
  • “Our data highlight the need for research into therapeutic maneuvers to reduce anti–interleukin-10 titers — for example, by means of B-cell and plasma-cell depletion (e.g., anti-CD19, anti-CD20, anti-CD38, or CD19 chimeric antigen receptor [CAR] T-cell therapy),29-31 plasma exchange, or blockade of the neonatal Fc receptor.32“

My take: Historically, in younger patients (6 or younger) and those with more severe inflammatory bowel disease, it has been common to evaluate for monogenetic diseases which may require different treatment approaches. For similar reasons, assessing for neutralizing autoantibodies against interleukin-10 is likely to become part of routine care.

Related study: Q Zhang Q, Shakweh E, Sharip M et al. The Lancet Gastroenterology & Hepatology, 2026; 0. Open Access! HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype–phenotype association study Key findings:

  • Among 43,762 patients with IBD (21 839 with Crohn’s disease and 21 923 with ulcerative colitis or IBD unclassified), HLA-DRB1*01:03 carriage was observed in 2009 (4·6%) patients with IBD and associated with multiple severe outcomes …including colonic resection in patients with Crohn’s disease (odds ratio 1·35), colectomy in patients with ulcerative colitis or IBD unclassified (1·99), and perianal disease in both patients with Crohn’s disease (1·65) and patients with ulcerative colitis or IBD unclassified (1·70)

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“Real-World” Impact of Vitamin D for Patients with Inflammatory Bowel Disease

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JA Sninsky et al. Clin Gastroenterol Hepatol 2026; 24: 1666-1674. Open Access! The Real-World Impact of Vitamin D Supplementation on Inflammatory Bowel Disease Clinical Outcomes

Methods: This was a retrospective cohort study of adult patients (n=5021) with IBD seen in the national Veterans Health Administration system from 2000 to 2023. The researchers used 3 different methods to try to determine causality of improved outcomes with supplementation of Vitamin D.

  1. “Difference-in-differences (DiD) approach to compare changes in clinical outcomes before and after vitamin D testing between patients who did and did not receive supplementation”
  2. “The regression discontinuity design leveraged the clinical threshold of 30 ng/mL serum 25-hydroxyvitamin D, comparing outcomes in patients just lower than and just higher than this cutoff, who are assumed to be otherwise similar”
  3. “The inverse probability weighting method adjusted for confounding by weighting patients based on their likelihood (propensity) of receiving vitamin D15“

Key findings:

  • The median 25-hydroxyvitamin D level was 23 ng/mL, and 41% received vitamin D supplementation
  • Vitamin D supplementation was associated with reduction in IBD-related emergency department visits by 2.17% (34.4% relative risk reduction; P = .007), hospitalizations by 2.64% (53.18% relative risk reduction; P = .003), and corticosteroid prescriptions by 1.29% (25.13% relative risk reduction; P = .066)

Discussion:

  • “Collectively, our data strongly suggest that vitamin D supplementation reduces the risk of IBD flare, underscoring its promise as an effective adjunctive therapy in clinical practice.”
  • “Vitamin D deficiency is prevalent among patients with IBD and is strongly linked to poor clinical outcomes, including higher rates of hospitalization and surgery. Patients with IBD are 64% more likely to be vitamin D deficient compared with healthy control subjects.29“
  • “Vitamin D deficiency is prevalent among patients with IBD and is strongly linked to poor clinical outcomes, including higher rates of hospitalization and surgery. Patients with IBD are 64% more likely to be vitamin D deficient compared with healthy control subjects.29“
  • “Although these findings support a strong association between vitamin D deficiency and worse clinical outcomes, they do not address whether supplementation itself mitigates the risk of adverse events, because disease severity confounds this relationship.33 Our study fills this knowledge gap and provides rigorous real-world data to support the effectiveness of vitamin D supplementation.”

My take: There have been large studies (eg. VITAL) study showing that Vitamin D supplementation does not help most people in the general population. In addition, many individuals with IBD who have low Vitamin D levels may see improvement in Vitamin D status by treating the IBD (without Vitamin D supplement). Yet, studies like this one by Sninsky indicate that Vitamin D supplementation is associated with improved outcomes in this retrospective cohort; the study methods likely indicate a causal effect of supplementation; however, a prospective randomized controlled study would be more definitive.

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Oral Vancomycin For Pediatric Inflammatory Bowel Disease

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S Ancona et al. J Pediatr Gastroenterol Nutr. 2026;82:1416–1426. Effectiveness and safety of oral vancomycin in non-primary sclerosing cholangitis paediatric inflammatory bowel disease

Background: “Oral vancomycin (OV) has limited usage in paediatric inflammatory bowel disease (PIBD) with reported efficacy in primary sclerosing cholangitis (PSC-PIBD), acute severe colitis as part of quadruple-antibiotic regimen, and very early-onset IBD. This study evaluates OV effectiveness and safety as a single-agent in non-PSC PIBD.”

Methods: Retrospective, single center study with 31 children (median age 15.1); the presence of PSC and C diff were exclusion criteria. There were  23 ulcerative colitis (UC), 4 IBD-unclassified (IBDU) and 4 Crohn’s disease. OV was started at 250 mg for patients ≥30 kg or 125 mg for those <30 kg and administered four times daily (QDS) or three times daily (TDS). The majority were receiving concomitant medications: steroids in 16%, biologics in 32%, 5-ASA in 74%, and thiopurines in 42%.

Key findings:

  • Clinical and biochemical remission was achieved or maintained in 17/31 (55%), with 15/17 reducing/stopping other treatments and two remaining on OV monotherapy
  • At 1-month faecal calprotectin dropped from 686 to 60 μg/g in responders (p = 0.001) but remained high in nonresponders
  • Responders (Group 1) continued OV for a median of 7.0 months (IQR 2.5–23.5), maintaining consistently low PUCAI and FC levels throughout a median follow‐up of 19.0 months. After discontinuation, three relapsed and restarted OV,recapturing remission in 2/3.
  • Responders had lower baseline clinical disease activity
  • No serious adverse events occurred. No vancomycin-resistant enterococcus (VRE) colonization was seen

My take: This study’s vancomycin responders (55%) had significant improvement within four weeks. This is in agreement with other studies indicating that antimicrobial regimens may be helpful in a significant subset of children with inflammatory bowel disease. Larger prospective studies are warranted.

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Real-life Study of Ustekinumab for Pediatric Crohn’s Disease (REALITI Study)

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SJ Steiner et al. J Pediatr Gastroenterol Nutr. 2026;82:1242–1250. Open Access! Effectiveness and safety of ustekinumab in pediatric Crohn’s disease: Results of the REALITI study

This retrospective study used prospectively-collected data from the ImproveCareNow (ICN) registry for pediatric patients. Overall, 479 patients with CD were treated with ustekinumab, 348 pediatric patients and 131 young adults; most were biologic-exposed (pediatric, 98.9%; young adult, 95.4%).

Key findings:

  • At week 52, clinical remission was achieved by 47.3% (125/264) of pediatric patients and 44.8% (39/87) of young adults, and CF (corticosteroid-free) clinical remission by 41.3% (109/264) and 39.1% (34/87), respectively
  • At Week 52 (observed case), among patients with moderately-to-severely active CD, clinical remission was achieved by 36.9% (41/111) of pediatric patients and 34.3% (12/35) of young adults, and CF clinical remission by 31.5% (35/111) and 28.6% (10/35), respectively.
  • Ustekinumab was well tolerated, with no new safety signals identified; however, a majority (89.4%) of the pediatric patients were 12–17 years old and most (76.5%) weighed ≥40 kg. Thus, further evaluations of ustekinumab in younger pediatric patients with CD and in those weighing <40 kg are still needed.
Observed case analysis of clinical effectiveness endpoints at Week 52 in (A) all patients with CD treated with ustekinumab, and (B) patients with moderately-to-severely active CD treated with ustekinumab.

My take: Studies indicate that newer selective IL-23 agents like risanizumab outperform ustekinumab. However, ustekinumab has FDA approval* for patients 2 years and older. In addition, there are several generic versions of ustekinumab which are less expensive than the newer agents. As such, I anticipate it will continue to be used.

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*There has been recent approval recent of Stelara (ustekinumab) for the treatment of pediatric patients 2 years and older with moderately to severely active Crohn’s disease. Here’s a link: Johnson & Johnson (JNJ) Gains FDA Approval for Pediatric Crohn’s Disease Treatment

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

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