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:
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:
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.
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.
C Strong, ACG 10/28/25: Long-Term PPI Treatment Linked to Higher Risk for Early-Onset CRC Before Age 50
An excerpt:
“Long-term treatment with proton pump inhibitors (PPIs) is independently associated with an increased risk for early-onset colorectal cancer (EOCRC) among individuals aged younger than 50 years, according to study results presented at the American College of Gastroenterology (ACG) 2025 conference…”
“Researchers reviewed data from the National Inpatient Sample from 2016 to 2020. Individuals were aged 18 to 49 years and had a main diagnosis of colorectal cancer (CRC)…Investigators identified PPI exposure through diagnostic codes indicating long-term use (Z79.891) or adverse effects (T45.4X5A/D)….
“Of the 7140 hospitalizations for patients with EOCRC aged younger than 50 years, 1056 (14.8%) reported long-term PPI treatment. After multivariable adjustment, PPI users had a 41% increased risk for EOCRC vs individuals without PPI use (adjusted odds ratio [aOR], 1.41…”
My take: More studies will be needed to determine if this link between PPI use and early onset CRC is truly significant. Many prior associations between PPI and other health conditions on observational studies have not held up with well-controlled studies. There was no increased risk of cancer in a previous randomized control trial (see below).
Related blog posts:
JO Bamidele et al. Annals Int Med 2025; https://doi.org/10.7326/ANNALS-25-015. The Mediterranean Diet for Irritable Bowel Syndrome: A Randomized Clinical Trial
Methods: Randomized noninferiority clinical trial (n=139 Adults from UK) — 6 weeks of the MD (Mediterranean diet) (n = 68) versus TDA (traditional diet advice) (n = 71). Primary end point was the proportion achieving clinical response, defined as 50-point or greater reduction in IBS Symptom Severity Scale (IBS-SSS).
Traditional dietary advice’s main elements are to “adopt sensible eating habits
and avoid excess fatty foods, spicy foods, processed foods, caffeine, fizzy drinks, and alcohol. The principal components of the MD are a diet rich in fruit, vegetables,
pulses (aka legumes), whole grains, nuts, fish, and olive oil.”
Key findings:
My take: I agree with the authors: The Mediterranean diet “represents a viable first-line dietary intervention for IBS.”
Related blog posts:
J-W Yang et al. Gastroenterology, Volume 169, Issue 5, 958 – 969.e5. Open Acces! Efficacy of ACupuncTure in Irritable bOwel syNdrome (ACTION): A Multicenter Randomized Controlled Trial
This ACTION study enrolled 280 patients (18-75 yrs) with IBS-D in a multicenter randomized controlled trial in 6 hospitals in China. “For the sham acupuncture group, blunt-tipped placebo needles with a similar appearance to real needles were used over the adhesive pads with no skin penetration. Five fixed pairs of non-acupoints (10 stimulation points in total) away from meridians or conventional acupoints were used.”
Key finding:
My take: Acupuncture, especially given its safety, is a reasonable therapy for IBS-D; though, it is not recommended in recent pediatric guidelines. “The rub” in many locations is finding qualified practitioners.
Related blog posts:
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:
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:
M Plassmeyer et al. Journal of Allergy and Clinical Immunology 2025; Dupilumab Opens a Therapeutic Window in Food Protein Induced Enterocolitis Syndrome by un-licensing dendritic cells
Thanks for Ben Enav for this reference.
Methods: This was a two-part study: “(i) a detailed single-patient case of wheat-triggered, endoscopy-confirmed colitic FPIES treated with dupilumab 300 mg subcutaneously every two weeks and (ii) a prospective follow-up of seven additional FPIES patients all of whom initiated dupilumab for approved comorbidities. Serial flow cytometry quantified dendritic-cell OX40L and CD8+ CRTH2+ T-cell subsets before and after treatment; open food challenges assessed clinical tolerance.”
Key Findings:
My take: Dupilumab appears to be a promising medication for FPIES and warrants further study. If confirmed to be effective, it is likely to be targeted to those with approved comorbidities and those with more severe presentations.
Related blog posts:
HH Lee et al. Clinical Gastroenterology and Hepatology 2025; 23, 2102 – 2114. Open Access! Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists
Methods: Meta-analysis of 17 randomized controlled trials in 8871 adults with moderate-severe UC. The authors calculated the ratio of odds ratio of achieving remission with active drug vs placebo, in TNF antagonist–naïve vs TNF antagonist–exposed patients.
Key findings:
Discussion:
My take: This study suggests that JAK inhibitors are a good choice for secondary therapy after anti-TNF agents. Other factors, besides efficacy, including safety, extraintestinal manifestations, and cost, have to be considered as well.
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.
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:
Key Concepts:
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:
gutsandgrowth 
06160-8/asset/17e8b821-1efa-4c66-adce-db270f9e7629/main.assets/fx1_lrg.jpg){kind=link}