IBD Shorts: Ustekinumab in Kids, Subcutaenous Infliximab, Nutrition Highlights

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MT Dolinger et al. J Crohns Colitis 2022.  doi: 10.1093/ecco-jcc/jjac055. Online ahead of print. Outcomes of Children With Inflammatory Bowel Disease Who Develop Anti-Tumor Necrosis Factor Induced Skin Reactions

In this retrospective study, among those who developed skin reactions to anti-TNF agents, 71 (64%) continued anti-TNF and 40 (36%) switched to ustekinumab (UST). Key findings:

  • Switching to UST had a higher rate and odds of resolution of skin findings (29/40 (73%) vs. 24/71 (34%); p <0.0001) and combined remission (21 (52%) vs. 22 (31%); p=0.03) vs. continuing anti-TNF at 6 months

PJ Smith et al. J Crohns Colitis, jjac053, https://doi.org/10.1093/ecco-jcc/jjac053 Open Access: Efficacy and Safety of Elective Switching From Intravenous to Subcutaneous Infliximab (Ct-P13): A Multi-Centre Cohort Study

Patients (n=181) on established maintenance IV infliximab who switched to SC CT-P13 were included in this retrospective multi-centre cohort study. Key findings:

  • Treatment persistence rate was high (N=167, 92.3%) and only 14 patients (7.7%) stopped treatment during the follow-up period. There were low rates of immunogenicity with no change in clinical disease activity indices or biomarkers

Link: Crohn’s and Colitis Congress 2022 Nutritional Highlights (Nutritional Therapy for IBD Website). This website has a summaries, and links to extensive information (videos/posters) from recent IBD meeting.

Sunrise in Sandy Springs (4/9/22) -no filter

Lessons Learned from Children In the Hepatitis B Virus Research Network

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SJ Schwarzenberg et al. JPGN 2022. 74: 431-433. Lessons Learned from Children Enrolled into the Hepatitis B Virus Research Network Multi-Center Prospective Study

This NIDDK-funded Hepatitis B Research Network (HBRN) was established in 2009 and enrolled 362 patients. 97% of participants were born in countries where HBV is endemic or in North America to mothers born from these countries.

Key points:

  • Due to revised criteria for ALT values, most pediatric patients have elevated ALT and do not meet the definition of immune-tolerant
  • Spontaneous flares (ALT >400 in males and >350 in females) in untreated children…did not lead to hepatic decompensation
  • Hepatocellular carcinoma was not identified in this cohort, though HBRN centers reported historical experiences. Only one patient developed cirrhosis over 4 years of followup.

Clinical Recommendations from Authors:

  • Screen for HBV in children with unexplained serum aminotransferases regardless of immunization history
  • Screen for HBV in children with normal aminotransferases if they or their parents are from an area where HBV is endemic or other risk factors
  • In those with HBV, monitor aminotransferases and HBV levels every 6 months
  • Obtain genotype in children with HBV
  • Consider treatment if ALT >2 x ULN over 3-6 mo. Treatment should follow AASLD guideline
  • Recommend AGAINST treatment at the start of a flare
  • Recommend counseling to promote healthy weight and avoidance of at-risk alcohol use

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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.

Prospective Study: Transanal Irrigation For Neurogenic Bowel

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J Fernandez et al. JPGN 2022; 74: 454-459.

This prospective study (n=80) expands on previous observations regarding the use of a transanal irrigation device for neurogenic bowel management.

Key points:

  • The neurogenic bowel dysfunction (NBD) score improved at both time points (<6 months, >6 months) by 14 and 13 points respectively. 94% and 98% had improved NBD score at time 1 and time 2 respectively
  • Patient satisfaction was high, though 8 patients discontinued device early on due to either discomfort or poor results
  • NBD score can used to monitor treatment effectiveness

Related blog posts:

IBD and Chronic Recurrent Multifocal Osteomyelitis: Paradoxical Association with anti-TNF Therapy in Some Cases

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MJ Dushnicky et al. JPGN 2021; 73: 626-629. Pediatric Patients with a Dual Diagnosis of Inflammatory Bowel Disease and Chronic Recurrent Multifocal Osteomyelitis

This article describes a retrospective review of seven patients with a dual diagnosis of inflammatory bowel disease (IBD) and chronic recurrent multifocal osteomyelitis (CRMO). In their cohort 4 of 6 were receiving anti-TNF therapy at the time of CRMO diagnosis. Misleading statements from this article:

  1. The triad of IBD, CRMO and psoriasis has not been reported previously to their knowledge
  2. “It seems unlikely that anti-TNF-alpha therapy would promote its [CRMO] development”

In JPGN Reports (not available on pubmed), Cordesse et al (JPGN Reports; November 2020 – Volume 1 – Issue 2 – p e007) identified the association of IBD, CRMO and psoriasis; in addition, they identified a paradoxical reaction to anti-TNF-alpha therapy; in this case series of three patients, anti-TNF-alpha therapy triggered CRMO and stopping anti-TNF-alpha therapy led to resolution of CRMO in two of the cases.

In a response to a letter to the editor (Hochman JA. JPGN 2022; DOI: 10.1097/MPG.0000000000003407. Faulty Information Regarding CRMO and IBD), Dushnicky et al (DOI: 10.1097/MPG.0000000000003433) note that JPGN Reports is not available on Pubmed; however, the articles that have described this association are near the top of a google search if one looks for “IBD, CRMO and Psoriasis.” Interestingly, in their response to the letter to the editor, the authors did not amend their claim that anti-TNF therapy is unlikely to promote CRMO despite being furnished with information showing that it can. In my view, the situation with CRMO is similar to psoriasis which can be treated with anti-TNF therapy and can paradoxically be caused by anti-TNF agents as well.

My take:

  1. CRMO is important to recognize due to its association with IBD and to realize that antibiotics are not an effective treatment.
  2. Anti-TNF-alpha agents can cause CRMO in some patients.
  3. In 2022, a web browser search (eg Google), in addition to Pubmed, is probably worthwhile when claiming that this is the first case of xyz ‘to our knowledge.’
Bahamas (from a friend)

Firearms: #1 Cause of Pediatric Deaths & Households with Guns =More Deaths

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AL Andrews et al. Pediatrics (2022) 149 (3): e2021052739. Pediatric Firearm Injury Mortality Epidemiology

Key points:

  • In 2019, firearm injuries surpassed motor vehicle collisions to become the leading cause of death for youth aged 0 to 19 years in the United States.
  • Approximately 60% of firearm-related deaths are homicides, 35% are suicides, and 4% are due to unintentional injuries
  • In 2015, the U.S. accounted for over 90% of all firearm deaths among children ages 0-14 years in high income countries.

DS Studdert et al. Annals Intern Med 2022; https://doi.org/10.7326/M21-3762. Open Access: Homicide Deaths Among Adult Cohabitants of Handgun Owners in California, 2004 to 2016

This retrospective cohort study followed 17.6 million adult residents of California for up to 12 years.

Key findings:

  • Overall rates of homicide were more than twice as high among cohabitants of handgun owners than among cohabitants of nonowners (adjusted hazard ratio, 2.33).
  • These elevated rates were driven largely by higher rates of homicide by firearm (adjusted hazard ratio, 2.83).
  • Among homicides occurring at home, cohabitants of gun owners had sevenfold higher rates of being fatally shot by a spouse or intimate partner (adjusted hazard ratio, 7.16); 84% of these victims were female.

My take: Gun ownership increases the likelihood of firearm-related deaths.

AAP Website: Gun Violence Prevention Advocacy Toolkit

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Latest Research: Modest Drinking Does NOT Confer Cardiac Benefits

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KR Biddinger et al. JAMA Netw Open. 2022;5(3):e223849. doi:10.1001/jamanetworkopen.2022.3849. Open Access: Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease

NY Times Analysis of This Study: Does Moderate Drinking Protect Your Heart? A Genetic Study Offers a New Answer.

An excerpt:

“There is no level of drinking that does not confer heart disease risk. The risk is small if people have an average of seven drinks a week when compared with none. But it increases quickly as the level of alcohol consumption rises”

“The study, which may help resolve medical disputes over the effects of alcohol on the heart, involved sophisticated analyses of the genes and medical data of nearly 400,000 people who participate in the U.K. Biobank”

“Some researchers have reported that drinking modestly protects the heart because moderate drinkers as a group have less heart disease than those who drink heavily or those who abstain. Dr. Aragam and his colleagues also saw that effect. But the reason, they report, is not that alcohol protects the heart. It is that light to moderate drinkers — those who consume up to 14 drinks a week — tend to have other characteristics that decrease their risk, like smoking less, exercising more and weighing less than those who drink more heavily and those who do not drink.“

“Many earlier studies of alcohol consumption and heart health were observational, meaning the subjects were followed over time to see if the amount of drinking was linked to heart health. Such studies are only able to find correlation but not causation, researchers say. But the Biobank study’s use of Mendelian randomization is more suggestive of causality, and so its results might carry more weight.”

My take: Light alcohol consumption is NOT beneficial for your heart.

Distant Kite Boarder, Isle of Palms, SC

Pediatric Capsule Endoscopy Curriculum Study

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UP Phatak et al. JPGN Reports 2022. 3: e130. Open Access: Pediatric Web-based Video Capsule Endoscopy Curriculum: A Pilot Study to Determine the Ability to Implement a Standardized Educational Curriculum

In this pilot study, 12 individuals completed a web-based curriculum for VCE proficiency.

Key finding:

  • Participants showed significant improvement in knowledge (P = 0.041) and photo recognition posttests (P = 0.015). All participants who completed the curriculum found it helpful and reported that they would recommend it to their colleagues

The discussion notes that “Studies have demonstrated that competence with VCE develops in an endoscopist after reading 10–15 VCE studies (6,10). There are some newer guidelines that suggest that this number may be higher…[and] it requires continuous practice. Pediatric gastroenterologists may feel their skills are not adequate when VCEs are not performed on a consistent basis at their institution”

Website for VCE Training: Pediatric Capsule Endoscopy Curriculum Study

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Early Antibiotics -Minimal Risk for Crohn’s Disease

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Previous studies have shown an association between the early use of antibiotics and an increased risk of inflammatory bowel disease. A recent study examined all the children born in Denmark from 1995-2009 and followed them up to 2013 via a prospectively maintained database.

A Mark-Christensen et al. Inflamm Bowel Dis 2022; 28: 415-422. Early-Life Exposure to Antibiotics and Risk for Crohn’s Disease: A Nationwide Danish Birth Cohort Study 

During a median 9.5 years (9.3 million total person-years), CD was diagnosed in 208 of 979,039 children.

Key findings:

  • Antibiotic use in the first year of life was associated with a higher risk of CD (adjusted hazard ratio, 1.4)…with the highest risk with ≥6 courses of antibiotics (adjusted hazard ratio, 4.1)
  • The cumulative risk of CD at the 11th birthday for children exposed to antibiotics in their first year of life was 0.16% compared to 0.11% for children unexposed to antibiotics in their first year of life. 

My take: This study indicates that antibiotics (and/or serious infections) are associated with an increased the risk of pediatric Crohn’s disease but the absolute risk is very low. We still have a lot to learn about how environmental exposures, including diet, infections, antibiotics, and pollution, contribute to the increasing prevalence of inflammatory bowel disease.

Related blog posts:

From Atlanta Botanical Gardens -Thanks to Jennifer for this picture

Health Benefit from Disease State: Sucrase-Isomaltase Deficiency

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It is well-recognized that genetic mutations that persist often confer some advantages. For example, sickle cell trait (but not disease) provides protection against malaria.

A recent study shows potential health benefits in those with sucrase-isomaltase deficiency: MK Andersen, L Skotte, E Jorsboe et al. Gastroenterol 2022; 162: 1171-1182. Open Access: Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts

Methods: “The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings”

Key findings:

  • Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index ( –2.0 kg/m2; P = 3.1 × 10–5), body weight (–4.8 kg; P = 5.1 × 10–4), fat percentage (–3.3%; P = 3.7 × 10–4), fasting triglyceride (–0.27 mmol/L; P = 2.3 × 10–6), and remnant cholesterol (–0.11 mmol/L; P = 4.2 × 10–5).
  • The metabolic profile “was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers” (0.056 mmol/L; P = 2.1 × 10–26), and partly by reduced sucrose uptake, but not lower caloric intake.
  • “These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.” 

My take: It should not be surprising that a genetic condition that results in limited sucrose intake would have health benefits. Perhaps correcting this condition will result in unexpected health issues similar to health issues that can develop in those with celiac disease after institution of a gluten-free diet (Gastroenterol 2013; 144: 912-17).

Related blog posts:

Graphical Abstract:

Expert Advice: De-Prescribing Proton Pump Inhibitors

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LE Targownik et al. Gastroenterol 2022; 162: 1334-1342. Open Access: AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review

Background: “Proton pump inhibitors (PPIs) are among the most commonly used medications in the United States, if not the world. Observational studies have demonstrated that PPI use has increased over time and that 7%–15% of patients use these medications at any time, with the prevalence increasing to 40% for patients 70 years or older…In a large observational study examining ambulatory visits of PPI users, nearly two-thirds had no clear indication for PPI use.”

Some of the best practice advice:

  • Best Practice Advice 2 All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient’s primary care provider.
  • Best Practice Advice 3 Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI.
  • Best Practice Advice 4 Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation.
  • Best Practice Advice 5 Patients with known Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing.
  • Best Practice Advice 7 Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing.
  • Best Practice Advice 10 The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PAAEs (PPI-associated adverse events).

My take: There are a lot of individuals who could benefit from de-prescribing PPIs.

Related blog posts:

Thanks to Susan for this picture which shows why our neighborhood is covered in a fine yellow dust.