R Michael, J Tozer. N Engl J Med 2024;390: e53. Small-Bowel Intussusception in an Adult
The authors describe the presentation/resolution of a 57 yo with a small bowel intussusception due to a fibroblastic polyp lead point.
Video: Reduction of Intussusception (may be behind a paywall)
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M Chehade et al. NEJM 2024;390:2239-2251 Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age
This study provides published data that has been referenced previously at time of FDA approval and prior meetings (see posts: Dupixent Approved in Younger Children (15 kg+), Dupixent for Eosinophilic Esophagitis (1-11 yrs) and Clinical Diagnosis of Rumination from DDW Tweets).
Methods:
Key findings:
My take: Dupilumab is an effective option for eosinophilic esophagitis.
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TC Tang et al. JPGN 2024;78:1317–1328. Proton pump inhibitors, antibiotics, and atopy increase the risk of eosinophilic esophagitis in children with esophageal atresia
In this retrospective study (2005-2020) with 184 children, key findings:
Discussion: “This is congruent with the emerging evidence in the general pediatric population that there is an increased risk of EoE development in individuals who undergo acid suppressive therapy. A possible explanation for these findings is that acid suppressants inhibit gastric parietal cell function and elevate the gastric pH, thereby impairing peptic digestion of dietary allergens, potentiating sensitization, and facilitating the development of allergic diseases like EoE.” Other potential explanations could include PPIs could increase mucosal permeability and/or contribute to dysbiosis.
“Hence, the routine use of PPIs for the first year of life as recommended by the current guidelines may need to be revisited..”
My take: This study shows a clear association of PPIs with development of EoE in this cohort. Due to the study design, it is difficult to be confident regarding causality due to possible selection bias (patients who received PPIs may be those with more predisposition to EoE). Nevertheless, this study suggests that prolonged use of PPIs, even in groups at risk for reflux damage, needs to be carefully considered and possibly directed by objective markers of reflux.
Related blog posts:
H Szajewska et al. JPGN 2024; https://doi.org/10.1002/jpn3.12280. Open Access! Early diet and the risk of coeliac disease. An update 2024 position paper by the ESPGHAN special interest group on coeliac disease
Key points:
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AJ Sanyal et al. NEJM 2024; DOI: 10.1056/NEJMoa2401755. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis
Background/Methods: “Dual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction–associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibrosis” was studied in “48-week, phase 2 trial, we randomly assigned adults with biopsy-confirmed MASH.” (n=293)
“Dual agonism of glucagon receptor and GLP-1 receptor may be more effective than GLP-1 receptor monoagonism for treating MASH, because the extrahepatic benefits of GLP-1 receptor agonism (glucose control, reduced appetite, and weight loss) are combined with direct hepatic effects (increased energy expenditure, lipolysis, and mobilization of hepatic fat) associated with glucagon receptor agonism.”
Key findings:
The discussion notes that “in a phase 2 trial, treatment with the GLP-1 receptor monoagonist semaglutide resulted in a significantly higher percentage of patients with MASH resolution than placebo but not in a significantly higher percentage of patients with improvement in fibrosis stage.26” Thus, the improvement in fibrosis, which was seen in this study with survodutide,will need to be examined in future studies.
My take: Earlier this year, the selective thyroid hormone receptor beta agonist resmetirom gained conditional approval from the Food and Drug Administration as the first pharmacotherapy for MASH with moderate-to-advanced liver fibrosis.5 It looks like there will be a number of pharmacologic agents available in the coming years. Cost and availability will be ongoing concerns. In addition, determining when/how these agents will be used in the pediatric population will not be clear for quite a long time.
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B Bokemeyer et al. Inflamm Bowel Dis 2024; 30: 746-756.
Methods: 3277 adult biologically-unexposed CD patients starting therapy with VEDO or anti-TNF were consecutively enrolled in 45 IBD centers across Germany (2017-202). This was a non-randomized, observational study with prospectively collected data.
Findings:
The discussion describes the strengths and limitations of this study. As it is not a randomized control trial, there can still be selection bias and confounding even with propensity scoring that was done in this study. The authors note that in a prior analysis of RCTs comparing infliximab to vedolizumab in CD patients, that infliximab had higher efficacy for induction and maintenance, though the clinical remission rates were only modestly improved at 1 year. (L Peyrin-Biroulet et al. BMC Gastroenterol 2022; 22: 291).
Recent expert guidance (2024) has favored infliximab and risankizumab over other advance therapies in CD patients who have not had previous biologic therapies (see: Comparative Evidence and Positioning Advance Therapies for Inflammatory Bowel Disease).
My take: This study shows that vedolizumab is a good advanced therapy for patients with Crohn’s disease without prior therapy. Among those with a clinical response at 14 weeks, the treatment durability was particularly impressive in this cohort.
It would be great to see an RCT in children with CD comparing IFX to VEDO. Treatment persistence is even more important in younger patients.
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NBC News 5/14/24: Wegovy users keep weight off for 4 years, new analysis finds
“The 17,604-patient trial tested Wegovy not for weight loss but for its heart protective benefits for overweight and obese patients who had preexisting heart disease but not diabetes. Participants were not required to track diet and exercise because it was not an obesity study…”
“Patients in the trial, called Select, lost an average of nearly 10% of their total body weight after 65 weeks on Wegovy. That percentage weight-loss was roughly sustained year-on-year until the end of about four years, where weight loss stood at 10.2%…”
“A third new analysis on Select published by Novo on Tuesday showed that the heart protective benefits of Wegovy to patients in the trial occurred regardless of their weight before starting on the drug and regardless of how much weight they lose on it.”
“The weight loss in the heart trial was less than the average of 15% weight loss in earlier Wegovy obesity studies”
Related blog posts:
B Constant et al. AJG 2024; DOI: 10.14309/ajg.0000000000002851. Insurer-Mandated Medication Utilization Barriers are Associated With Decreased Insurance Satisfaction and Adverse Clinical Outcomes: An Inflammatory Bowel Disease Partners Survey
Key findings: In this longitudinal survey with 2017 patients, 72% experienced an insurer-mandated barrier, most commonly prior authorizations (51%). Fifteen percent were denied an IBD medication by their insurer, 22% experienced an insurance-related gap in therapy, and 8% were forced by their insurer to switch from an effective medication. Several insurance barriers were linked to negative downstream clinical outcomes, including prior authorizations associated with corticosteroid rescue (odds ratio [OR] 2.24]), forced medication switches associated with continued disease activity (OR 3.28), and medication denials associated with IBD-related surgery (OR 8.92).
Related blog posts:
S Danese et al. Lancet Gastroenterol Hepatol 2024; 9: 133-146. Efficacy and safety of 48 weeks of guselkumab for patients with Crohn’s disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial
In this phase 2 randomised, multicentre, double-blind trial with 309 adults, the authors report on the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study. Key findings:
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L Keefer et al. Gastroenterology 2024; 166: 1182-1189. AGA Clinical Practice Update on Pain Management in Inflammatory Bowel Disease: Commentary
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It turns out that Duracell has been trying to reduce button battery ingestions for a few years (in 2020) by coating the sides of the batteries with a bitter tasting no-toxic chemical. I only recently found out about this. “Duracell uses Bitrex, a non-toxic, man-made substance that’s considered the world’s most bitter, to create the coating. The coating is harmless if consumed, but it’s designed to encourage children to spit out the battery immediately.” (Anecdotally, one of our endoscopy nurses said she tried the battery and she did not think it was very bitter.) The packaging is also very difficult to open without scissors.
Advice from their website: “If your child swallows a battery, go to the emergency room.
If you have other questions or concerns, call 1-800-498-8666 or visit www.batteryingestionhotline.com.”
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gutsandgrowth 