Tag Archives: Crohn’s disease

Video Capsule Endoscopy in VEO-IBD — Is the Juice Worth the Squeeze?

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S-I Hagiwara et al.  Inflammatory Bowel Diseases, 2025; izaf144, https://doi.org/10.1093/ibd/izaf144. Open Access! Feasibility and Safety of Small Bowel Capsule Endoscopy in Very Early-Onset Inflammatory Bowel Disease: A Multi-Institutional Study

This article shows that video capsule endoscopy (VCE) (aka small bowel capsule endoscopy [SBCE]) is feasible in children with very early-onset inflammatory bowel disease (VEO-IBD). There were 82 patients (median age, 3.8 years; median body weight, 13.0 kg) who underwent 104 SBCEs. All capsules were deployed endoscopically. Gastrointestinal patency was assessed in 95% of procedures, most commonly using patency capsules (70%).

Key findings:

  • Observation of the entire small intestine was achieved in 100 (96.1%) patients
  • Of the remaining 4 patients, 3 could not undergo a complete observation of the entire small intestine due to battery depletion, and 1 had the capsule retained in the stomach
  • Abnormal small bowel findings were observed in 42% of patients, with aphthae being the most common (34%), followed by ulcers (18%)

In their discussion, the authors note that due to young age, the capsules and the patency capsules required endoscopic deployment (best in duodenum). Thus, most patients received general anesthesia or intravenous sedation twice within a short period.

The authors note that “SBCE has been reported to be superior to MRE in detecting superficial mucosal activity… [and] offers a radiation-free, relatively well-tolerated, and highly sensitive method for mucosal evaluation in VEO-IBD.”

My take: Given the typical use of a patency capsule and thus the need for two separate anesthesia dates, I doubt the “juice is worth the squeeze” in utilizing SBCE for most patients VEO-IBD.

Related blog posts:

Useful repurposing of phone booth in Cotwolds, UK

Postoperative Outcomes with Tofacitinib Following Colectomy for ASUC and Real-World Outcomes for Upadacitinib in Crohn’s Disease

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C Larson et al. Clin Gastroenterol Hepatol 2025; 23: 2263-2271. Postoperative Outcomes in Tofacitinib-Treated Patients With Acute Severe Ulcerative Colitis Undergoing Colectomy

This  was a multicenter, retrospective, case-control study of patients hospitalized with ASUC who underwent colectomy, comparing patients treated with tofacitinib (n=41) prior to colectomy with infliximab-treated controls (n=68).

Key findings:

  • Compared with tofacitinib-treated patients, infliximab-treated patients had higher overall rates of overall (44 [64.7%] vs 13 [31.7%]; P = .002) and serious (19 [27.9%] vs 3 [12%]; P = .019) postoperative complications

My take: This study supports the safety of JAK inhibitor therapy for ASUC. It showed a significantly lower rate of overall postoperative complications in ASUC patients treated with tofacitinib compared with infliximab; the authors note that “these findings can likely be extrapolated to upadacitinib, a selective JAK inhibitor, given its similar mechanism of action.”

J Devi et al. Clin Gastroenterol Hepatol 2025; 23: 2281-2291. Open Access! Real-World Effectiveness and Safety of Upadacitinib in Crohn’s Disease: A Multicenter Study

Related blog posts:

Spotlight: AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

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Yesterday’s post (AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease) summarized the following article:

The associated “Spotlight” provides useful a graphic summary. Here is most of the information:

AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

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FI Scott et al. Gastroenterology, Volume 169, Issue 7, 1397 – 1448; Open Access! AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

The guideline panel agreed on 16 recommendations. This highly-detailed report provides a comprehensive, patient-centered, evidence-based approach to the pharmacologic management of adult patients with moderate-to-severely active CD. Table 1 summarizes this lengthy 53-page report. Tomorrow’s post will be the “spotlight” summary which presents the recommendations in easier to read graphic.

Key Points:

The guidelines are overall very helpful. They identify higher efficacy medications and recommend them. In addition, they support the use of combination therapy with thiopurines (which are less frequently used in pediatrics). It is interesting that the sixteenth recommendation clashes with prior expert recommendations. The sixteenth recommendation in this report makes no recommendation on using endoscopic surveillance compared to symptomatic clinical remission. Most experts advise “treat-to-target” therapy approaches.

In the discussion of this, the authors state the followiing:

“Recent position statements from an international consortium of experts have advised that longitudinal targets for the management of IBD should include not only clinical remission but also endoscopic resolution of inflammation.31 Several studies have demonstrated that patients who achieve endoscopic remission (vs those with ongoing endoscopic activity) have favorable long-term outcomes…

There are limited RCTs assessing whether there is actual benefit in systematically treating toward endoscopic remission target vs symptomatic remission targets (ie, testing whether the target has been achieved, followed by algorithmic treatment adjustment, including escalating index therapy, adding an immunomodulator, followed by switching to an alternative advanced therapy and surgery). There was significant heterogeneity among the 2 reviewed studies, both in terms of the advanced therapy used, algorithms for therapy modification, and the cadence and frequency of endoscopic monitoring that challenge interpretation. Based on the significant uncertainty of evidence with regard to improving maintenance of remission or reducing the risks of adverse events, the guideline panel could not make a recommendation in relation to selecting endoscopic targets over clinical targets.

It is worth emphasizing that in both of the included trials, the majority of individuals in the endoscopic healing arms were not able to meet the goal of endoscopic healing despite an algorithmic approach. For example, in STARDUST, only 11% of individuals achieved endoscopic remission.149…There are specific patient populations, such as those who have recently undergone intestinal resection,155 in which endoscopic evaluation may be particularly valuable in clinical decision making...

The benefit of a monitoring strategy incorporating biochemical monitoring over clinical monitoring alone was demonstrated in the CALM trial,152 and has been addressed in previous AGA guidelines on the role of biomarkers in patients with CD.12“

My take: These “living” guidelines are likely to be quite influential in selecting Crohn’s disease therapy. In pediatrics, ImproveCareNow provides a similar role of guiding treatment.

Related blog posts:

Guidelines for UC:

Crohn’s Disease:

Outcomes of Hematopoietic Stem Cell Transplant in Monogenic Inflammatory Bowel Disease

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A Baccarella et al. Clinical Gastroenterology and Hepatology; 2025; 23: 2242 – 2252. Open Access! Outcomes of Allogeneic Hematopoietic Stem Cell Transplant in Monogenic Inflammatory Bowel Disease

This was a retrospective single-center (CHOP) study of 25 children with monogenic IBD who underwent Hematopoietic Stem Cell Transplant (HSCT) (2012-2022).

Key findings:

  • Seventy-two percent of patients had Crohn’s Disease, and 28% were classified as IBD-unspecified. Ninety-two percent of patients had VEO-IBD, 56% presenting under age 1
  • At most recent follow-up, 92% of patients achieved sustained medication-free remission of IBD and 60% with prior ostomy underwent re-anastomosis. There was 100% survival at a median follow-up of 3 years
  • There was significant improvement in growth, hospital days, and severe infections
Disease activity scores at the time of IBD presentation, immediately prior to transplant, 1-year post-transplant, and at most recent follow up if ≥2 years since transplant.

Discussion points:

  • “Delay of HSCT with the goal of obtaining remission of IBD prior to transplant may prove to be determinantal, as outcomes of HSCT are in general improved for younger patients,20 and medical remission is often unattainable for more severe forms of monogenic IBD. Within our cohort, 32% of patients had moderate or severe disease at the time of transplant despite medical optimization. None of these patients developed intestinal GVHD, which was a rare event in our total cohort”
  • “HSCT is not without risk, and complications occurred in our cohort, at rates typical of other IEI cohorts”
  • “The selection of patients who would benefit from HSCT requires multidisciplinary discussion.”

With regard to patient selection, one item that was not included in the discussion was the one patient excluded from their analysis who had a TTC7A gene defect. In the results section, it was explained that the patient with “TTC7A was subsequently excluded as transplant was performed for the indication of SCID alone, rather than treatment of intestinal disease.” More discussion on this point is merited as many centers would NOT have a patient with TTC7A undergo HCST specifically because it cannot correct the underlying bowel disease.

Also, it was noted that one patient with CTLA4 deficiency had undergone HSCT prior to the discovery of the genetic defect. With the more widespread use of genetic testing available now, this discovery may have obviated the need for HSCT as treatment with abatacept is typically effective.

My take: Overall, the authors present impressive results for HSCT for monogenic IBD and strengthen the need for genetic testing in those with early onset disease and those refractory to treatment.

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.

How to Best Use Steroids for Inflammatory Bowel Disease

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JD Feuerstein et al. Clin Gastroenterol Hepatol 2025; 23: 2068-2082. Open Access! Appropriate Use and Complications of Corticosteroids in Inflammatory Bowel Disease: A Comprehensive Review

Steroids are commonly used and misused for inflammatory bowel disease. This article reviews best practices, steroid formulations/dosing, and potential complications.

  • For moderate to severe ulcerative colitis (in adults), the authors recommend treatment with 40 mg of prednisone daily. Patients with ASUC (acute severe ulcerative colitis) should be treated with 60 mg of IV methylprednisolone for 3 to 5 days, after which rescue therapy should be initiated
  • Use of budesonide is recommended as an option for many clinical situations to minimize steroid adverse effects. These situations include mild-moderate UC failing to respond to mesalamine, ileal CD and older patients
  • Postoperative complications: “In the postoperative period, patients treated with CS had a higher risk of both infectious complications (aOR, 3.69; 95% CI, 1.24–10.97) and major infectious complications (aOR, 5.54; 95% CI, 1.12–27.26) [Abrerra et al].135  Subramanian pooled data from 7 studies showing that preoperative CS use is associated with increased postoperative complications (OR, 1.41; 95% CI, 1.07–1.87) as well as infectious complications.

The authors note that corticosteroids “remain widely available and are an effective short-term option for induction of remission in patients with active UC or inflammatory CD. However, their well-described and significant safety profile warrants proactive strategies to limit their use through non-systemic formulations, short-term exposures, steroid-sparing maintenance options, and most recently, complete steroid avoidance strategies.”

My take: Continuing steroids when they are not effective prior to potential surgery (eg. ASUC) remains a frequent problem. Sometimes, it is difficult to know it they are helping some.

Randomized Control Trial of the Modified Crohn’s Disease Exclusion Diet (CDED)

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RS Boneh et al. Clin Gastroenterol Hepatol 2025; 23: 2001-2011. Open Access! Modified Crohn’s Disease Exclusion Diet Maintains Remission in Pediatric Crohn’s Disease: Randomized Controlled Trial

In this “DIETOMICS” study with 56 children with mild-to-severe Crohn’s disease, after a 2 week exclusive enteral nutrition (EEN) diet, 30 patients were randomized to CDED and 26 to EEN.

Diet intervention: The CDED group followed 3 diet phases over 24 weeks: phase 1 (weeks 3–8) supplemented with 50% PEN; phase 2 (weeks 9–14) with 25% PEN, as described previously16; and phase 3 (weeks 15–24) with gradual introduction of more foods, including 1 and 2 free meals per week from weeks 15 and 18, respectively.17 Patients in EEN group received 8 weeks of EEN followed by gradual introduction of free diet with 25% PEN up to week 24.

Key findings:

This study with a relatively small number of enrolled patients had a lot of variables in dietary parameters. “An additional potential confounder in this study is the use of IMM therapy. Although both groups were recommended to initiate IMM therapy from weeks 4 to 5 to maintain remission, several CDED patients opted for monotherapy with CDED and preferred to delay medication initiation. Interestingly, 90% of patients on CDED without IMM therapy were in remission at week 14 and 100% were in remission at week 2” (possibly impacting decision not to use IMM).

My take: This study adds another piece of information to the puzzle on dietary therapy for Crohn’s disease. The authors note the following: “while CDED shows promise as a standalone therapy in some cases, in more severe cases it may be more appropriately as an adjuvant to top-down treatment with early anti-TNF.4 Recent research and guidelines advocate for a top-down approach (anti-TNF ± nutrition) for more severe disease, emphasizing the integration of anti-TNF therapy with nutrition.8,29 This approach is crucial during critical growth stages, as the conventional step-up method may lead to ineffective use of IMM with prolonged steroid exposure and growth issues.12“

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

Proximal Ileal Crohn’s Disease is Harder to Treat

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K Takenaka et al. Clin Gastroenterol Hepatol 2025; 23: 1991-2000. Open Access! Inadequate Efficacy of Biologics for Treating Proximal Ileal Lesions in Crohn’s Disease: A Prospective Multicenter Study

This multicenter prospective study (n=253) examined efficacy of treatment in patients with proximal ileal disease using balloon-assisted enteroscopy (BAE). The recruited patients had a mean disease duration of 4 years. 52% were naive to biologic treatment at baseline.

Key findings:

  • At baseline, 74 patients (29.2%) had proximal ileal ulcerations without terminal ileal ulcerations
  • At week 26, after treatment with anti-TNF therapy (n=103), ustekinumab (n=99) or vedolizumab (n=51), endoscopic remission was achieved in 91 patients (36.0%). Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum
  • The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared with the colon (63.4%) and terminal ileum (56.7%)
  • After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P = .0126 for hospitalization and P = .0014 for surgery). In contrast, there was no significant differences in hospitalization and surgery associated with endoscopic activity vs remission in the colon or terminal ileum.

Discussion: Residual “proximal ileal ulcerations … are associated with a poorer prognosis…Additionally, we confirmed that proximal ileal inflammation is less responsive to biologic therapies compared with colonic inflammation. Although the reasons for this disparity remain unclear”

My take: Balloon-assisted enteroscopy is not frequently used in the setting of inflammatory bowel disease, particularly in pediatrics. MRE is typically used to follow proximal small bowel disease, though it has less sensitivity for luminal mucosal disease.

Related blog posts:

Comprehensive ACG Clinical Guidelines for Crohn’s Disease (2025)

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GR Lichenstein et al. The American Journal of Gastroenterology 120(6):p 1225-1264, June 2025. Open Access!!  ACG Clinical Guideline: Management of Crohn’s Disease in Adults

Yesterday and Today I am highlighting two adult clinical guidelines both of which are equivalent to up-to-date textbook chapters with specific recommendations; both are open access. In addition, the articles have accompanying author podcasts. Thanks to Ben Gold for these references.

Selected Management Recommendations:

  • Table 1, #3: We suggest against requiring failure of conventional therapy before initiation of advanced therapy for the management of CD
  • Table 1, #13: We recommend combination therapy of intravenous infliximab with immunomodulators (thiopurines) as compared with treatment with either immunomodulators alone or intravenous infliximab alone in patients with CD who are naive to those agents
  • Table 1, #33: In patients with high-risk CD, we recommend anti-TNF therapy to prevent postoperative endoscopic recurrence

Key Concepts:

  • Table 2, #9: Symptoms of CD do not correlate well with the presence of active inflammation and therefore should not be the sole guide for therapy. Objective evaluation by endoscopic or cross-sectional imaging should be undertaken periodically to avoid errors of under- or over-treatment.
  • Table 2, #14: The 10-year cumulative risk of major abdominal surgery in CD is 40%–55%, although recent studies performed in the biologic era suggest that the 10-year risk may have decreased to 30%. The 10-year risk of a second resection after the first is 35%, although again more recent studies suggest that this may have dropped to closer to 30%.
  • Table 2, #15: In CD, the 5-year rate of symptomatic postoperative recurrence is ∼50%.
  • Table 2, #29: Small bowel imaging should be performed as part of the initial diagnostic workup for patients with suspected CD.
  • Table 2, #31: Because of the absence of radiation exposure, magnetic resonance enterography should be used preferentially in young patients (younger than 35 years) and in patients in whom it is likely that serial exams will need to be performed.
  • Table 2, #38: Mucosal healing as determined by endoscopy is a goal of therapy. Scoring systems are available to measure the endoscopic disease activity and may be used to monitor response to therapy.
  • Table 2, #41: Antibiotics are not an effective treatment for luminal inflammatory CD and should not be used as a primary therapy.

My take: Given the rapid changes in available therapies, it would be optimal to make these collaborative guidelines (AGA, ACG, NASPGHAN) available online with frequent updates (similar to HCVguidelines.org).

Related blog posts:

Why Pediatric Patients Need Higher Dosing of Infliximab

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E Stenke et al. Inflamm Bowel Dis 2025; 31: 2331-2337. Higher-Dose Infliximab Induction Achieves Better Maintenance Trough Levels in a National Pediatric IBD Cohort—A Retrospective Study

In this single center retrospective study from Ireland, the authors examined 122 patients (93 with Crohn’s disease [CD], 18 with ulcerative colitis [UC], 1 with IBDU) who received infliximab and had prospectively-collected data. The earlier cohort 2018-2019 received 5 mg/kg/dose and the later group 10 mg/kg/dose. Both groups had proactive therapeutic drug monitoring (pTDM).

Key findings:

  • The 5 mg/kg group, compared to the 10 mg/kg group, was less likely to have target pre-third TLs (6% vs 80%, P < .001) with the stated goal of >/= 15 microgm/mL
  • Fewer patients in the 5 mg/kg than 10 mg/kg group had pre-fourth TLs ≥5 µg/mL (6/48 [12.5%] vs 28/50 [56%], P < .001; mean [SD] TL 3.5 [6.3] vs 10.0 [9.9], P < .001)
  • Concurrent immunomodulator therapy was more common in the 5 mg/kg group (43% compared to 24%)
  • 80% of patients were still receiving infliximab at 1 year including 87% of patients with CD and 54% with UC
  • The higher dose group had a lower CRP at 1 year followup. 26% of patients receiving the lower dose had a CRP > 5 mg/L compared with 9% in the higher dose group.
  • Some other measures of long term outcome (eg. IFX durability, clinical remission) were slightly better but did not reach statistical significance (see below)

Discussion Points:

  • “Our data show higher rates of below-target infliximab levels during and after induction in the 5 mg/kg group. Higher rates of dose escalation in this group during the first year resulted
    in similar dosing regimens…Thus, the similar infliximab durability and clinical outcomes
    at 1-year follow-up reflect early-dose optimization leading to dose equalization between the 2 groups, rather than a lack of benefit to higher dosing regimens”
  • “Our data affirm that proactive TDM with pre-emptive dose escalation restores
    below-target infliximab TLs and sustains clinical response…Indeed, in our cohort, some patients with low IFX levels pre-third dose were given their fourth dose 6 weeks later, rather
    than the standard 8 weeks. Without proactive TDM results, our rate of suboptimal TLs pre-fourth and during maintenance therapy would have been higher in both groups”
  • “Rates of immunomodulator use in the 10 mg/kg group were lower than in the earlier cohort of 5 mg/kg, reflecting changes in clinical practice over time”

My take:

  1. This study shows that 94% of pediatric patients did NOT achieve adequate levels of infliximab at the pre-third dose with “standard” therapy. This was true even with 43% of the lower dose cohort receiving combination therapy (which often helps improve pharmacokinetics)
  2. Proactive therapeutic drug monitoring helped mitigate the clinical outcomes, especially in the lower dosed cohort
  3. “Children with IBD treated with the historic standard dose of 5 mg/kg induction are at increased risk of pharmacokinetic treatment failure related to high rates of suboptimal TLs”

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.