Upadacitinib for Crohn’s Disease: U-ENDURE Study

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R Panaccione et al. Clin Gastroenterol Hepatol 2025; (In press) Open Access! Upadacitinib Maintenance Therapy in Crohn’s Disease: Final Results From the Randomized Phase 3 U-ENDURE Study

Methods: Clinical responders to 12 weeks of upadacitinib 45 mg once daily (QD) induction were randomized (1:1:1) to receive upadacitinib 15 mg QD (n = 221), upadacitinib 30 mg QD (n = 229), or placebo (n = 223) as maintenance therapy for 52 weeks

**This study presents data from the entire cohort (n=673); a previous report from ENDURE-3 analyzed data on 502 patients (though findings were nearly identical). EV Loftus et al. N Engl J Med 2023; 388:1966-1980 (Related post: Landmark Study: Oral Biologic for Crohn’s –Upadacitinib)

Key findings:

  • At week 52, more upadacitinib-treated vs placebo patients achieved CDAI clinical remission (upadacitinib 15 mg, 36.2% and upadacitinib 30 mg, 51.5% vs placebo, 15.2%)
  • The rates of endoscopic response were 27.3% for upadacitinib 15 mg and 40.7% for upadacitinib 30 mg vs 7.2% for placebo
  • Herpes zoster infections occurred more frequently in the upadacitinib groups compared with placebo; all were nonserious, and most involved a single dermatome
  • In U-ENDURE, no dose-dependent risk for MACE, VTE, or malignancy (excluding NMSC) was observed during the 52-week maintenance period

My take: Upadacitinib is a effective in a good number of patients with with moderately to severely active Crohn’s disease who have been refractory to other advanced therapies.

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Warnings of Hepatitis B Vaccine Policy Shift

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Despite the enormous benefits of hepatitis B vaccination, it appears that this administration has its sights on changing the policy of administration at birth.

NY Times 9/16/25: C.D.C. Vaccine Advisers May Limit Hepatitis B Shots for Newborns

An excerpt:

Committee members, some of whom are vaccine skeptics, are likely to recommend restricting the use of the shots at birth or delaying them until later in childhood…

“Unless the mother is hepatitis-B-positive, an argument could be made to delay the vaccine for this infection,” Martin Kulldorff, the committee’s chair, said at its previous meeting in June.

Vaccine experts at the C.D.C., who normally would be deeply involved in preparing for this week’s meeting, have been sidelined and given no more information than the public about the meeting’s agenda or possible outcomes…

Before 1991, when newborns were not all vaccinated for hepatitis B, about 20,000 babies became infected each year. Routine immunization at birth cut the number of newborn infections … There are now fewer than 20 children per year who acquire the disease from their mothers.

Only about half of the cases before 1991 were a result of transmission from an infected mother. The other half “weren’t getting it from becoming sex workers, and they weren’t getting it from being intravenous drug users,” Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, said…

From 2015 to 2017, about 21,000 infants were born to pregnant women with hepatitis B antibodies, but fewer than half were identified through prenatal screening, according to the C.D.C.

My take: If routine immunization at birth is stopped, there will be a lot more hepatitis B infections and subsequent complications. Some infections will be acquired at birth and some later due to missed opportunities to provide protection later on.

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Brooklyn Botanic Garden

What Caught My Eye in a Recent Anti-IL23 Commentary

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This recent commentary on the all-subcutaneous induction and maintenance treatment with guselkumab, an anti-IL23 agent, reviewed the GRAVITI study. Related post: Guselkumab for Crohn’s Disease: Pivotal GRAVITI Study

However, what captured my attention was the last sentence: “The convenience of subcutaneous induction enhances patient friendliness, positioning guselkumab as a strong market contender. Could an oral anti–IL-23 formulation be the next game changer?14“

“Johnson & Johnson (NYSE: JNJ) today announced positive topline results from ANTHEM-UC, a Phase 2b study of icotrokinra (JNJ-2113), the first investigational targeted oral peptide that selectively blocks the IL-23 receptor, in adults with moderately to severely active ulcerative colitis (UC)…

In the ANTHEM-UC study (n=252), three doses of once daily icotrokinra were tested with all meeting the primary endpoint of clinical response at Week 12. A response rate of 63.5% for patients treated with the highest dose of icotrokinra was achieved at Week 12 versus 27% for placebo (p<0.001). Further, 30.2% of patients treated with the highest dose of icotrokinra demonstrated clinical remission at Week 12 versus 11.1% of patients who received placebo (p<0.01). Remission and response rates continued to improve through Week 28.

  • Clinical response is defined as decrease from baseline in the modified Mayo score by greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
  • Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy.”

My take: It would be terrific for patients with inflammatory bowel disease (and other immune-mediated diseases) to have another excellent oral therapy. A prior study of plaque psoriasis indicated that an oral IL-23 medication is feasible (Related post: In Trials: An Oral IL-23 Antagonist Peptide).

Related joke (regarding “caught my eye” in the title of this post):

A man who lived in a block of apartments thought it was raining and put his head out the window to check.  As he did so a glass eye fell into his hand. He looked up to see where it came from in time to see a young woman looking down. “Is this yours?” he asked.

She said, “Yes, could you bring it up?” and the man agreed. On arrival she was profuse in her thanks and offered the man a drink. Shortly afterwards she said, “I’m about to have dinner.  There’s plenty; would you like to join me?” He readily accepted her offer and both enjoyed a lovely meal. As the evening was drawing to a close the lady said, “I’ve had a marvelous evening.  Would you like to stay the night?”  The man hesitated then said, “Do you act like this with every man you meet?”

“No,” she replied, “only those who catch my eye.”

The Manneporte by Claude Monet (at the Metropolitan Museum of Art)

Global Evidence of Gastric Cancer Prevention with Helicobacter pylori Eradication

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Several recent articles have confirmed the benefits of H pylori eradication on reducing the risk of gastric cancer. This is in both Western and Eastern populations.

In this retrospective study from Nordic countries (Denmark, Sweden, Norway, Finland, and Iceland), researchers followed outcomes among ~700,000 people treated for H. pylori infection. The incidence of gastric adenocarcinoma was twice that of the general population in the first 5 years after treatment, likely reflecting H. pylori–related carcinogenesis that already was underway, but after 11 years, the incidence fell to that of the general population and remained there.

Discussion points:

  • The results of this study from 5 entire Western countries are in line with systematic reviews from Asian populations, indicating that H pylori eradication reduces the risk of gastric cancer
  • In addition, it has been proposed that eradication of H pylori might increase the risk of esophageal adenocarcinoma, but our recent study based on the NordHePEP found no such increase (Ref: Gastroenterology. 2024; 167:485-492.e3)

In this population-based study with more than 900,000 individuals, gastric cancer incidence and mortality rates were significantly lower in H pylori-treated individuals than in the general population.

In this meta-analysis of 11 randomized trials and 13 cohort studies researchers compared outcomes in treated and untreated H. pylori–positive adults. In both groups of studies, gastric cancer incidence was 40% lower in people who underwent H. pylori eradication. All but two of these studies were from eastern Asia.

 “In 2025, the IARC Working Group has issued a new report reaffirming H pylori eradication as a globally actionable and cost-effective intervention for the primary prevention of GC.18…Also, addressing the global public health challenge of antibiotic resistance remains essential, necessitating the development of susceptibility-guided or empirically optimized regimens tailored to local resistance patterns.

My take (borrowed from the commentary): “Despite the challenges, collectively, the emerging evidence from diverse populations reinforces the significant benefits of H pylori eradication in reducing GC incidence and mortality. These findings continuously support that H pylori eradication remains an effective preventive strategy across demographic settings, highlighting its relevance as a critical public health measure globally.”

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IBS Impact: Survey Reveals Daily Life Struggles

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AGA GastroNews, AGA IBS in America survey reveals IBS major burden despite advances in treatment (8/7/25):

Methods: The Harris Poll on behalf of AGA in 2024, among 2,013 U.S. adults age 18+ who have been diagnosed by a health care provider with IBS-C (1,005) or IBS-D (1,008). In addition, U.S. health care provider research was conducted online among 600 health care providers including gastroenterologists (n=200), primary care physicians (PCPs, n=200), gastroenterology nurse practitioners (NP)/physician assistants (PA) (n=100), and PCP NP/PAs (n=100)

Key findings:

  • IBS symptoms interfere with patients’ productivity at work/school for nearly 11 days per month on average
  • IBS symptoms disrupt personal activities eight days per month on average
  • 69% say their symptoms make them feel like they’re not “normal”
  • 77% avoid situations where bathroom access is limited.
  • 72% find it difficult to plan activities due to unpredictable symptoms.
  • 72% stay home more often because of their symptoms

My take: This sample of patients with IBS likely has more severe symptoms than a more general population of patients with IBS. Nevertheless, it highlights the impact of IBS symptoms on daily living.

Link: AGA IBS Toolkit

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Westminster Abbey, London


Is a High Protein Diet Beneficial and Safe?

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There has been a lot of hype about the benefits of a high protein diet. In a recent substack article (8/31/25) , Eric Topol reviews the data on this (for adults).

Here’s the link:Our Preoccupation With Protein Intake

Key points:

  • “The pervasive call for higher protein intake stems from the assertion that people are not getting adequate amounts in their diet, namely the 0.8 g/kg/day recommend by the National Academy of Medicine and the World Health Organization….
  • Regarding the need to increase protein intake 2-3 fold per day, Stuart Phillips, a leading expert on protein, energy, and building muscle mass, who is a professor at McMaster University in Canada, said “It’s baloney. But there’s a generation, particularly young men, and now an increasing number of young women, who are absolutely brainwashed by what they hear online”…there are no data to support more than 1.6 g/kg/day of protein intake.

Safety concerns:

  • “There are many observational studies that have raised the safety concerns for high-protein intake, particularly derived from animal protein, for increased risk of type 2 diabetes, cardiovascular disease, and higher all-cause mortality. A prospective study of ~44,000 women in Sweden followed for 15.7 years found an association of high-protein diet with heightened cardiovascular risk.”
  • A “high protein intake is dangerous for people with kidney disease, present in 1 of 7 adults, but 9 of 10 people with reduced kidney function are unaware of it.”

My take (borrowed from Dr. Topol): “The body of evidence about protein does not provide support [for] very high protein intake, certainly not in excess of 1.6 g/kg/day…there is no way to store protein in the body…Resistance training is the principal driver for building muscle mass and strength, not high protein intake.” While this article focuses on adults, the premise is similar in children; though, on a per kilogram basis, children need modestly higher amounts. (Reference: JL Hudson et al. Nutrients. 2021 May 5;13(5):1554. Dietary Protein Requirements in Children: Methods for Consideration)

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How Often Esophageal Coins Pass Into the Stomach

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P Quitadomo et al. Am J Gastroenterol 2025; 120: 1388-1390. “Insert-Coin”: A Prospective Study of Coin Ingestion in Children of Southern Italy

Thanks to Ben Gold for this reference.

This prospective study from Naples, Italy examined children 0-14 yrs of age with a coin ingestion (n=807). Children with coins in the proximal esophagus underwent endoscopic removal within 4 hours whereas those with middle to lower esophageal coins had re-evaluation after 12 hours before removal.

Key findings:

  • 52 of 807 (6.4%) had a coin retained in the esophagus, the remainder were in the stomach or beyond
  • 20 of 52 (38%) were located in the middle to lower esophagus (10 in each)
  • 13 of 20 (65%) coins in the middle to lower esophagus had spontaneous gastric passage
  • The mean age of patients with gastric passage (72 months) was higher than those without passage (48 months)

My take: Only 6% of patients in this study who had a coin ingestion had esophageal retention of the coin. In addition, one-fourth of those with esophageal coins had spontaneous passage into the stomach. This occurred only with the mid-distal esophageal coins; in this subset it occurred in 65%. Thus, in those with mid-distal esophageal coins, watchful waiting for ~12 hrs may be beneficial for patients. The ultimate primary prevention of this problem may occur with more widespread adoption of electronic payments.

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Agnes Northrup of Louis Tiffany Studio,
Tiffany Garden Landscape Window (1912)
at The Metropolitan Museum of Art
Agnes Northrup of Louis Tiffany Studio,
Autumn Landscape  (1923) at The Metropolitan Museum of Art

“Are Marathons and Extreme Running Linked to Colon Cancer?”

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NY Times 8/19/25: Are Marathons and Extreme Running Linked to Colon Cancer?

An excerpt:

A small, preliminary study found that marathoners were much more likely to have precancerous growths. Experts aren’t sure why…

Dr. Cannon, an oncologist with Inova Schar Cancer in Fairfax, Va., launched a study, recruiting 100 marathon and ultramarathon runners aged 35 to 50 to undergo a colonoscopy.

The results were staggering. Almost half the participants had polyps, and 15 percent had advanced adenomas likely to become cancerous. The rate of advanced adenomas was much higher than that seen among adults in their late 40s in the general population, which ranges from 4.5 percent to 6 percent, according to recent studies.

The research was presented at an American Society of Clinical Oncology conference but has not yet been published in a medical journal…

Dr. David Rubin, chief of gastroenterology and director of the Inflammatory Bowel Disease Center at the University of Chicago, said the study was important but limited. It lacked a control arm consisting of similar young adults who were not long-distance runners, he noted, and the family histories of colon cancer among the marathoners were not entirely known…

Runners often develop gastrointestinal symptoms that they dismiss as benign — so-called runner’s trots, for example. The symptoms can be caused by ischemic colitis, a condition that develops when blood flow to the colon is temporarily reduced as it is redirected to muscles in other parts of body (like a runner’s legs).

My take: While this is a small study, it indicates that extreme runners could have an increased risk of colonic polyps and cancer. If there are symptoms (especially rectal bleeding and weight loss), a low threshold for further evaluation is needed.

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View of Statue of Liberty from Governor’s Island

IBD Management in Pregnancy: Global Consensus

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U Mahadevan et al. Clinical Gastroenterology and Hepatology 2025 (published ahead of print). Open Access! Global Consensus Statement on the Management of Pregnancy in Inflammatory Bowel Disease

Addendum -updated reference: U Mahadevan et al. Clinical Gastroenterology and Hepatology 2025; 23: S1-S60. Open Access! Global Consensus Statement on the Management of Pregnancy in Inflammatory Bowel Disease

This is a 60 page open access article. Table 1 lists 34 “GRADE” statements and Table 2 lists 35 consensus statements. This article is also jointly published in the following:

  • Gut
  • Am J Gastroenterol
  • Inflammatory Bowel Diseases
  • Journal of Crohn’s and Colitis
  • Aliment Pharmacol Ther

For Moms:

For Babies:

My take: This is a useful reference –mainly helpful for gastroenterologists rather than pediatric providers.

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The Best Way to Judge Pediatric Poo

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J Orozco et al. Am J Gastroenterol 2025; 120: 1381-1387. Comparison of the Bristol Stool Scale and Modified Version for Children: Use by Providers vs Children

Thanks to Ben Gold for this reference.

Background: The modified Bristol Stool Form Scale for Children (mBSFS-C) removes #3 and #5 from the Bristol Stool Form Scale (BSFS), leaving only one normal image and shortening the options from seven to five.

Methods: Pediatric gastroenterology providers  (21 faculty, 11 fellows, 3 nurse practitioners)  and 200 children/families rated the same 35 stool photographs, reflecting diverse stool forms, using both scales. The order of photograph presentation and scale use were randomized.

Modified Bristol Stool Scale
Bristol Stool Chart

Key findings:

  •  Of 1,225 provider ratings using the mBSFS-C, 90.0% agreed with the provider’s modal ratings vs 77.8% using the BSFS.
  • Of 7,000 child ratings using the mBSFS-C, 84.6% agreed with the children’s modal ratings vs 71.8% using the BSFS.
  • Using providers’ modal ratings as the reference, all mBSFS-C photograph modal ratings matched between children and providers (35/35 photographs) whereas only 86% (30/35 photographs) matched with the BSFS.

Discussion:

  • “Unique and new in this study is the direct head-to-head comparison of the 2 scales (BSFS, mBSFS-C) when used by pediatric gastroenterology providers and children. Both the BSFS and mBSFS-C demonstrated excellent reliability…modal rating agreement was significantly poorer for the BSFS than for the mBSFS-C.”
  • “Almost 20% of the time expert raters using the BSFS (vs. 8% with the mBSFS-C) deemed a stool to be a different clinical delineation than that selected by the majority of their peers.”

Related editorial: Peter Lu, The American Journal of Gastroenterology 120(6):p 1267, June 2025. Is It Time to Scale Down the Bristol?

My take: The modified BSFS is easier and better. This study indicates it should be widely used for children but probably for adults too. As Dr. Lu’s editorial notes, “aren’t adults just big children?”

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