Category Archives: Gastroenterology

Modest Benefits of Early Advanced Therapies in IBD?

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R Lujan, R Buchuk et al. Gastroenterol 2024; 166: 815-825.Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort

Methods: All patients diagnosed with CD or UC in Israel (2005–2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort. The authors compared disease duration at biologics initiation (ie, 0–3 months, >3–12 months, >1–2 years, and >2–3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias.


Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. To attempt to adjust for patient characteristics, “essentially, each patient was cloned 4 times and 1 clone was assigend to each treatment strategy at baseline…[they were removed] subsequently if they did not receive the biologic within the acceptable time window.” Key findings:

  • In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2–3 years (31%) and 0–3 months (18%; P = .02; number needed to treat, 7.7)
  •  In CD, the 10-year probability of steroid dependency for the 0–3-month period (19%) differed both from the >2–3-year (31%; P < .001) and 1–2-year periods (37%; P < .001).
  •  In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods.
  • Similar trends were noted in the pediatric population.

Thus, overall, the study found that early initiation of biologics was associated only with a modest reduced risk of surgery and steroid dependency for Crohn’s disease. It was not found to reduce risk of colectomy or steroid dependency in UC.

My take: In my view, this study probably underestimates the benefits of early biologic therapy. Even though, lead time bias can skew interpretation, inadequately-treated disease likely leads to long-term damage. The associated editorial (pg 728) by Murphy notes that despite the sophisticated statistical methodology, all observational studies cannot fully control for unmeasured confounders.

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Colorado River Near Moab, UT

This past weekend there were two fun events in Atlanta -Porchfest (Virginia Highlands) and Midtown Garden Stroll. Porchfest featured more than 50 local bands.

Here’s a couple photos from the Midtown Garden Stroll:

Long Duration of Eosinophilic Esophagitis Associated with a Stiff Esophagus

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IK Araujo et al. Clin Gastroenterol Hepatol 2024; 22: 513-522. The Severity of Reduced Esophageal Distensibility Parallels Eosinophilic Esophagitis Disease Duration

This study of 171 adult patients (mean age 38 years) who had FLIP at time of an EGD determined the degree of esophageal distensibility and its association with eosinophilic esophagitis disease duration.

Key findings:

  • The median symptom duration was 8 (interquartile range, 3–15) years and diagnostic delay was 4 (interquartile range, 1–12) years
  • Symptom duration and diagnostic delay were negatively correlated with distensibility plateau (DP) (rho = –0.326 and –0.309; P values < .001)
  • Abnormal esophageal distensibility (DP ≤17 mm) was more prevalent with increased duration of symptoms (P < .004): 23% at <5 years to 64% at ≥25 years
  • Patients with ≥15 eos/hpf had significantly lower DP with greater symptom duration (P = .004), while there was not a significant difference among patients with <15 eos/hpf (P = .060).

My take: Longer duration of disease increases the risk of esophageal fibrosis and lack of distensibility. We need better tools to predict who is at most risk for developing fibrosis.

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Upadacitinib vs Ustekinumab for Ulcerative Colitis

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RS Dalal et al. Clin Gastroenterol Hepatol 2024; 22: 666-668. Comparative Effectiveness of Upadacitinib vs Ustekinumab for Ulcerative Colitis: A Multicenter Retrospective Cohort Study

This was a multicenter retrospective cohort study of adults with ulcerative colitis comparing upadacitinib (n=70) to ustekinumab (n=148). The upadacitinib-treated patients were all bio-exposed, had more advanced therapy failures, and higher baseline SCCAI (simple clinical colitis activity index).

Key findings:

  • Upadacitinib-treated patients had better outcomes: Clinical response of 82.9% vs. 63.5%, Steroid-free clinical remission 62.1 % vs. 34.7%, improvement in arthralgia 64.3% (9 of 14) vs 23.4% (11 of 47), and endoscopic remission 37.5% (9 of 24) compared with 15.9% (7 of 44).
  • The odds ratio (OR) after inverse probability of treatment-weighting were in favor of upadacitinib: Clinical response OR 2.39, SFCR OR 3.17, and endoscopic remission OR 5.10
  • Similar amounts of adverse effects were reported in each group

My take: Upadacitinib had better response rates within 52 weeks even though the patients receiving this medication had more advanced therapy failures. However, it is important to keep in mind the limitations of this retrospective study. The improved outcomes are in contrast to a study comparing another JAK inhibitor (tofacitinib) to ustekinumab in which the outcomes appeared equivalent (Tofacitinib vs Ustekinumab -Which is Better for Ulcerative Colitis?).

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Heron at Azalea Park (Sandy Springs, GA)

What is Mild Crohn’s Disease and How to Treat It

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S Elmasry, C Ha. Clin Gastroenterol Hepatol 2024; 22: 480-483. Evidence-Based Approach to the Management of Mild Crohn’s Disease

This article provides guidance on what is mild Crohn’s disease (CD) and suggested management. The authors note that there are limited randomized controlled trial data focusing on patients with mild CD.

Key points:

  • “Maintenance strategies often fall under the realm of supportive care. Therapeutic approaches need to factor clinical effectiveness, prevention of disease-related complications, risks of adverse events resulting from undertreatment or overtreatment and costs of care.”
  • For induction, the authors suggest budesonide 9 mg per day for 8 weeks with tapering, a tapering course of prednisone or sulfasalazine for colonic CD
  • In those with response to induction, the authors recommend supportive care including anti-diarrheal agents and dietary modifications. Ongoing monitoring is suggested including clinical symptoms and objective labs/biomarkers (every 12 weeks if CD activity and every year during remission)
  • In those without response or early relapse, the authors advocate for further evaluation for disease activity and alternative etiologies along with consideration of advanced therapies (f objective evidence of persistent activity)
  • “Accumulating evidence supports diets rich in fruits and vegetables with limited intake of foodstuffs containing saturated fats, ultraprocessed foods, artificial sweeteners, and emulsifiers.”
  • Advanced therapies “such as vedolizumab, ustekinumab, and risankizumab may be considered owing to favorable effectiveness and safety profiles…may be too cost-prohibitive to justify use for mild CD.”

My take: As younger patients are at increased risk for disease progression, the approach recommended in this article would have very limited application in the pediatric age group.

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Are Kids Different? TB Testing in Patients Receiving Biologics

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SL Lapp et. al. Clin Gastroenterol Hepatol 2024; 22: 420-422. Open Access! Yield of Serial Testing for Tuberculosis Exposure in Patients With Inflammatory Bowel Diseases: One Test is Not Enough

This “retrospective cohort study was conducted using data acquired from SPARC IBD, a component of the Crohn’s & Colitis Foundation’s IBD Plexus research platform. SPARC IBD is a prospective cohort study conducted at 18 US centers and includes more than 4000 patients.” The median patient age was 37 years.

Key findings:

  • Following an initial negative result in 687 patients, 269 patients received a second test (after an initial negative test), of which 5 were positive (1.9%), which was not significantly different from the prevalence with the first test
  • Oral steroids were associated with an increased proportion of indeterminate results, although not achieving statistical significance
  • The authors did not identify any potential risk factors for latent tuberculosis among the covariates investigated

Overall, the authors found “found that there is continued utility for the use of IGRA tests with patients receiving medication for IBD despite the declining incidence of tuberculosis in the United States. In addition to testing before administration of treatment, this study suggests serial testing may still be necessary because of a substantial rate of positive conversions among patients in the cohort.”

After reading this study, I did an informal survey from the physicians/APP in my group. As a group, we take care of approximately 1000 children with inflammatory bowel disease. Over the last 20 years, only one of my partners recollects having a true positive test result after an initial negative result. This particular patient who was asymptomatic received a 9 month course of isoniazid.

My take: There is a low yield of follow-up testing for tuberculosis, especially in pediatric patients with no exposure history or travel history. For our practice, this would be a good summer research project for a premed student, a resident or even a fellow. I would expect the yearly and cumulative costs of screening for latent tuberculosis in our practice to be quite high. A quick web search suggests that a single blood test costs ~$150 which would be $105,000 for 700 tests. However, the costs are much greater due to additional investigations related to indeterminate results.

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SC Infliximab versus Vedolizumab for Crohn’s Disease and for Ulcerative Colitis

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Peyrin‐Biroulet, L., Arkkila, P., Armuzzi, A. et al. BMC Gastroenterol 24, 121 (2024). https://doi.org/10.1186/s12876-024-03163-5. Open Access! Comparative efficacy and safety of subcutaneous infliximab and vedolizumab in patients with Crohn’s disease and ulcerative colitis included in randomised controlled trials. 

Methods: Studies included in the current analysis were parallel-group, randomised controlled trials (RCTs) that evaluated treatment with IFX SC, following induction therapy with IFX IV, or treatment with VDZ (either with VDZ IV or with VDZ SC [following IV induction therapy]). The authors identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ.

Key findings:

Crohn’s disease: Intravenous induction therapy with IFX demonstrated better efficacy compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year.

Comparison of IFX SC versus VDZ for key efficacy outcomes in patients with Crohn’s disease

Ulcerative colitis: Efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year.

Comparison of IFX SC1 versus VDZ for key efficacy outcomes in patients with ulcerative colitis

Safety: In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year.

Discussion Points:

  • The authors discuss some limitations of their study. “The GEMINI I, GEMINI II, and VISIBLE 1 trials were rated as being at high risk of bias for the category ‘other’ bias, because only patients who achieved a clinical response during induction went on to participate in the maintenance phase, which could potentially lead to a higher estimate of efficacy during the maintenance phase than if patients who did not achieve a clinical response were also included.”
  • The vedolizumab studies notably included a high proportion of patients who failed to respond to anti-TNFs. “All VDZ studies permitted enrolment of patients with prior TNFi failure, accounting for 47.5% of VDZ-treated patients overall.” Thus, in a true head-to-head study with patients unexposed to biologics, VDZ may achieve better results.

My take: This study indicates that SC infliximab (like IV infliximab) appears to be more effective than vedolizumab for patients with Crohn’s disease and similarly effective for ulcerative colitis, keeping in mind the aforementioned discussion points. While not evident in this study, vedolizumab has a superior safety profile.

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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.

How (In)Effective Are Prebiotics for Ulcerative Colitis

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Thanks to Mike Hart for this reference.

V Sinopoulou et al. Cochrane Database of Systematic Reviews 2024 March 20. Prebiotics for induction and maintenance of remission in ulcerative colitis.

This study included 9 RCTs involving a total of 445 participants. Key findings:

  • Though some of the study findings seemed to favor prebiotics, all evidence was of very low certainty.
  • “There may be no difference in occurrence of clinical relapse when adjuvant treatment with prebiotics is compared with adjuvant treatment with placebo for maintenance of remission in UC.”
  • “Adjuvant treatment with prebiotics may result in more total adverse events when compared to adjuvant treatment with placebo for maintenance of remission.  The evidence was of low certainty.”

My take: Currently, there is no solid evidence to recommend prebiotics in patients with ulcerative colitis.

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Maho Bay, St John

More Data Supporting Dietary Treatment for Irritable Bowel

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S Nybacka et al. The Lancet Gastroenterol Hepatol 2024; DOI: https://doi.org/10.1016/S2468-1253(24)00045-1. A low FODMAP diet plus traditional dietary advice versus a low-carbohydrate diet versus pharmacological treatment in irritable bowel syndrome (CARBIS): a single-centre, single-blind, randomised controlled trial

In this Swedish study with 294 randomized participants who had with moderate to severe I.B.S, 96 assigned to the LFTD (low FODMAPs with IBS advice) diet, 97 to the low-carbohydrate diet, and 101 to optimised medical treatment. Response was defined as a reduction of 50 or more in IBS-SSS compared with baseline.

Key findings:

  • Response rate after 4 weeks: 73 (76%) of 96 participants in the LFTD diet group, 69 (71%) of 97 participants in the low-carbohydrate diet group, and 59 (58%) of 101 participants in the optimised medical treatment group

The findings of this study were included in a recent NY Times Article (4/18/24): What’s the Best Way to Treat I.B.S.?

An excerpt:
“A new study suggests that certain dietary changes may be more effective than medication.. When she checked on the participants during the trial, one from the low-FODMAP group cried when she described how much better she felt on the diet. Another in the low-carbohydrate group said she “never in her life had felt so good in her stomach,” Dr. Nybacka said…

Dr. Chey said the study was well done and provided “real data” to support what many doctors have observed: That “diet therapy is at least as good and probably better” than medication.

My take: Dietary therapies and psychological therapies are underutilized in the management of IBS. For those using dietary therapies, counseling with a nutritionist is a good idea.

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Grand Canyon (from Seth Hochman)

AGA Guidance: GLP-1 Receptor Agonists Prior to Endoscopy

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JG Hashash et al. Clin Gastroenterol Hepatol 2024; 22: 705-707. Open Access! AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication

“GLP-1 RAs (eg, semaglutide, tirzepatide, exenatide, liraglutide, albiglutide, dulaglutide, and lixisneatide) mimic incretins, which are hormones released after eating that prompt glucose-dependent insulin release from the pancreatic islets, stimulate satiety centers, inhibit glucagon release, and result in diminished gastric emptying.”

Because GLP-1 RAs diminish gastric emptying, they can increase the risk of residual gastric contents prior to surgery and endoscopy.

AGA Recommendations:

  • “If patients taking GLP-1 RAs solely for weight loss can be identified beforehand, a dose of the medication could be withheld before endoscopy with likely little harm, although this should not be considered mandatory or evidence-based. Nevertheless, it is unclear
    if withholding the medication for only one dose would be reliably adequate for an individual’s gastric motility to return to normal. ..there is insufficient evidence to suggest this practice be performed for patients taking these medications to treat diabetes”
  • “Generally, in patients on GLP-1 RAs who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper
    and/or lower endoscopy.”
  • “When possible, placing patients on a liquid diet the day before sedated procedures may be a more acceptable strategy, in lieu of stopping GLP-1 RAs.”

My take: This guidance provides useful advice given the increasing use of GLP-1 RAs. If these medications are being used for obesity, holding a dose prior to endoscopy is a good idea.

Related article: S Sen et al. JAMA Surgery 2024;  doi:10.1001/jamasurg.2024.0111. Glucagon-Like Peptide-1 Receptor Agonist Use and Residual Gastric Content Before Anesthesia Key finding:  Use of a GLP-1 RA was independently associated with increased residual gastric content (1.5 mL/kg of clear liquids on gastric ultrasonography) on preprocedural gastric ultrasonography: 56% (35 of 62) in patients with GLP-1 RA use (exposure group) compared with 19% (12 of 62) in patients who were not taking a GLP-1 RA drug (control group).

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This is at the entrance to the Westside Reservoir Park.
I had the chance to go there as part of a Westside Beltline Tour in Atlanta.

This reservoir is as deep as the Statue of Liberty is tall and
can hold 2.4 billion gallons of water for the city of Atlanta

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.

Prokinetics Have Little Benefit for Gastroparesis

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WL Hasler et al. Clin Gastroenterol Hepatol 2024; 22: 867-877. Open Access! Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis

Methods: In this prospective study of patients (n=129) with suspected gastroparesis, the authors examined longitudinal outcomes focusing on responses to prokinetics and other therapies. This included gastroparesis diets and neuromodulators. Patients underwent validated gastric emptying testing (wireless motility capsule and gastric emptying scan) before recommending new treatments.

Prokinetics included dopamine antagonists, motilin agonists, acetylcholinesterase
inhibitors, and pyloric botulinum toxin injection.

Key findings:

  • “Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of
    gastroparesis.”
  • “Neuromodulators as the only new therapy decreased symptoms other than
    nausea and vomiting”
  • Combination therapy of a prokinetic with a neuromodulator appeared to be the most effective
  • Neuromodulators were mainly effective in those without delayed gastric emptying times

My take: Our therapies for gastroparesis are not very good. And, neuromodulators are likely to be more helpful than prokinetics.

Example of a gastroparesis diet: Cleveland Clinic Gastroparesis Diet (7 pages). Part of the diet recommendations are shown below.

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