Expert Guidance on Current Management of IBD (Part 1)

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A recent issue of Clinical Gastroenterology and Hepatology focused solely on the clinical features and management of inflammatory bowel disease. Even for those with expertise in IBD, there is a lot of useful information and concise reviews of what is known.

Here are some of my notes from this issue:

AN Ananthakrishnan et al. Clin Gastroenterol Hepatol 2020; 18: 1252-60. Changing Global Epidemiology of Inflammatory Bowel Diseases: Sustaining Health Care Delivery Into the 21st Century

Reviews risk factors and recommends the following as ways to lower risk of developing IBD for at-risk individuals:

  • Breastfeeding in infancy
  • Do not start smoking
  • Avoid vitamin D deficiency
  • Minimize non-steroidal anti-inflammatory drug use
  • Minimize antibiotic use especially for young children and during pregnancy
  • Encourage moderate physical activity, healthy weight, low stress and regular sleep
  • Diet high in fruit, vegetables, fiber, and fish

Reviews the epidemiology and notes that there has been a evidence of a decline in incidence in IBD in (at least) the Western world; however, because of compounding prevalence, it is expected that the number of individuals with IBD will continue to rise.  In Canada, for example, it is expected that the prevalence will rise from 0.7% in 2018 to 1% by 2030.

In newly industrialized countries, it is expected that rising incidence is going to substantially increase the global disease burden. The authors note the following as areas needed in research and clinical care to meet global IBD care burden:

  • tools for early diagnosis
  • early effective intervention to prevent irreversible bowel damage
  • precision medicine to select the right treatment for the right patient
  • need for less costly and more safe therapies
  • simple tools to monitor disease activity
  • primary disease prevention strategies, especially for those at high risk

CA Siegel, CN Bernstein. Clin Gastroenterol Hepatol 2020; 18: 1261-7. Identifying Patients With Inflammatory Bowel Diseases at High vs Low Risk of Complications

This article’s disease-stratification information overlaps with subsequent articles which detail the positioning of therapies for Crohn’s disease (CD) and ulcerative colitis (UC) respectively.

NH Nguyen, S Singh, WJ Sandborn. Clin Gastroenterol Hepatol 2020; 18: 1267-79. Positioning Therapies in the Management of Crohn’s Disease.

Some of the information summarized in this article:

Table 2 -Comparative Efficacy of Biologics for Moderate to Severe Active Crohn’s Disease (CD):

  • Infliximab: For induction: OR compared to placebo for remission: 5.90 (2.78-12.51); probability of remission 60%. For maintenance in those with clinical response: probability of remission SUCRA ranking: 48%; 0.68
  • Adalimumab: For induction: OR compared to placebo for remission: 3.80 (1.76-8.18); probability of remission 49%. For maintenance in those with clinical response: probability of remission SUCRA ranking: 58%; 0.97
  • Ustekinumab: For induction: OR compared to placebo for remission: 2.75 (1.76-4.32); probability of remission 41%.  For maintenance in those with clinical response: probability of remission SUCRA ranking: 39%; 0.36
  • Vedolizumab: For induction: OR compared to placebo for remission: 2.69 (1.36-5.32); probability of remission 40%.  For maintenance in those with clinical response: probability of remission SUCRA ranking: 42%; 0.52
  • Certolizumab pegol: For induction:  OR compared to placebo for remission: 1.36 (0.89-2.08); probability of remission 25%.  For maintenance in those with clinical response: probability of remission SUCRA ranking: 42%; 0.48

In deciding therapy, the authors specify factors that help classify as high-risk CD Table1):

  • Structural damage: large or deep mucosal lesions, fistula or perianal abscess, prior resections (especially if >40 cm)
  • Inflammatory burden: extensive disease involvement (ileal disease >40 cm or pancolitis), increased C-reactive protein, low albumin
  • Impact on quality of life: presence of stoma, >10 loose stools/week, lack of symptomatic improvement with prior biologics and/or immunomodulators, presence of anorectal symptoms, anemia, daily abdominal pain
  • Emerging predictors: antimicrobial antibody pattern, antimicrobial genetic peptide signature

Though the authors note a lack of adequate head-to-head comparative studies, they make some recommendations for treatment:

  • For severe disease, they suggest first-line therapy for CD would be infliximab or adalimumab in combination therapy regimen (with infliximab favored for higher disease severity)
  • For second-line therapy, they suggest ustekinumab for most patients in combination therapy or 2nd anti-TNF in those with loss or response due to immunogenicity or intolerance
  • For those with higher risk factors for adverse events (or preference) and moderate disease severity, the authors recommend vedolizumab as 1st line and ustekinumab as 2nd line.  For this same group with higher disease severity, they suggest ustekinumab as 1st line treatment.

Other key points:

  • In terms of risk of malignancy, the authors note that in a comprehensive systematic review of 23 RCTs of TNF-alpha antagonists in IBD, there was NO significant increase in the risk of malignancy with TNF-alpha antagonists.
  • In terms of combination therapy, the authors note that their has been an observed benefit which is “at least partly attributed to achieving a higher biologic trough concentration….no differences in efficacy of combination therapy vs infliximab were observed when evaluating patients by quartiles of infliximab trough concentration; however, currently this represents association rather than causation, and it is possible that superior remission rates drove higher trough concentrations, rather than vice versa.”

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.

Eight States with Increasing COVID-19 Problems

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States with unfavorable trends: Arizona, Arkansas, Florida, North Carolina, South Carolina, Tennessee, Texas, and Utah.  From Eric Topol Twitter feed:

Also recent modeling indicates that face masks lower transmission rate –from Reuters: Widespread mask-wearing could prevent COVID-19 second waves: study

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AGA Practice Guidelines: Probiotics NOT Helpful for Most GI Conditions

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Here is a link to the EPUB draft of AGA clinical report (G Su et al. Gastroenterology DOI: https://doi.org/10.1053/j.gastro.2020.05.059): AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders

Here is a link to the pre-draft technical review by GA Preidis et al. Gastroenterology DOI: https://doi.org/10.1053/j.gastro.2020.05.060 AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders

  • The report recommends NOT using probiotics outside of clinical trials for irritable bowel syndrome, Clostridium difficile infection treatment, Crohn’s disease, and gastroenteritis.
  • It recommends a specific probiotic for pouchitis and for prevention of necrotizing enterocolitis in preterm infants <37 weeks and 3 probiotics for patients who are receiving antibiotics (to prevent Clostridium difficile infection)

CNN summary: Probiotics don’t do much for most people’s gut health despite the hype, review finds

“While our guideline does highlight a few use cases for probiotics, it more importantly underscores that the public’s assumptions about the benefits of probiotics are not well-founded,” said Dr. Grace L. Su, a professor of medicine and chief of gastroenterology at the University of Michigan, Ann Arbor, in a news statement. She was the chair of the panel that issued the new guidance….

“The industry is largely unregulated and marketing of product is often geared directly at consumers without providing direct and consistent proof of effectiveness,” said the new guidelines. “This has led to widespread use of probiotics with confusing evidence for clinical efficacy,” it said…

“Not all probiotics are created equal. Some probiotic strains and mixtures are very effective for some types of diseases and should not be overlooked due to studies that lump all probiotics together as one”

My take: Probiotics are overhyped and underperform for most conditions. This report suggests that most people should NOT be taking probiotics.

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Wired: When Health Care Moves Online, Many Patients Are Left Behind

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Wired: When Health Care Moves Online, Many Patients Are Left Behind

An excerpt:
Amid the coronavirus pandemic, more of the nation’s medical care is being delivered by telephone or videoconference, as in-person care becomes a last resort for both doctors and patients. That’s a problem for tens of millions of Americans without smartphones or speedy home internet connections. For them, the digital divide is exacerbating preexisting disparities in access to health care…

Overall, as many as 157.3 million people in the US only have access to substandard download speeds. During the pandemic, roughly half of low-income American say they’re concerned about affording to pay their broadband and smartphone bills, according to April Pew Research data. In rural areas (where Pew figures suggest only 63 percent of residents have home broadband subscriptions), phone calls might be patients’ best option.

Related blog post: #NASPGHAN19 Impact of New Technology

Short Gut Diet -CHOA Approach

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Recently Kipp Ellsworth, with input from members of the nutritional team, developed our first institutional Short Gut Diet.

Per Kipp, this diet is “designed to facilitate digestion while minimizing abdominal pain and ostomy/stool output in our inpatients with truncated intestinal anatomy.  Previously, clinicians ordered a regular diet for our short gut patients, with parents and nurses providing oversight of the ordering process based on their knowledge of short gut diet precepts.  Obviously this non-standardized approach resulted in significant noncompliance, another onerous daily task for nursing, and a failure of inpatient short gut diet principles reinforcement.  I anticipate the new diet serving as an omnipresent education tool, reinforcing short gut diet precepts for patients and parents during their inpatient stays.”

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NY Times: Japan’s Secret Success with Coronavirus

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NY Times: Is the Secret to Japan’s Virus Success Right in Front of Its Face?

An excerpt:

In America, masks have become a weapon in the culture wars. In Japan, wearing one is no big deal, and deaths have stayed low…

Face coverings are nothing new here….
Yet a feared spike in cases and deaths has not materialized. Japan has reported more than 17,000 infections and just over 900 deaths, while the United States, with a population roughly two and a half times as large, is approaching 1.9 million cases and 110,000 deaths.

“Japan, I think a lot of people agree, kind of did everything wrong, with poor social distancing, karaoke bars still open and public transit packed near the zone where the worst outbreaks were happening,” Jeremy Howard, a researcher at the University of San Francisco who has studied the use of masks, said of the country’s early response. “But the one thing that Japan did right was masks.”…

The scientific evidence on whether a mask protects the wearer from infection is mixed. But experiments show that masks can be effective in blocking the emission of respiratory droplets that may contain the virus, even when someone has no symptoms of illness. And there is some evidence that infected people with no symptoms can still transmit the coronavirus.

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Huntingdon Lake, Sandy Springs (no image filters used)

Briefly Noted: Bleeding in Noonan Syndrome, Pets Help Children’s Emotional Health

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B Briggs et al. J Pediatr 2020; 220: 154-8.  This study confirmed a high rate of bleeding problems in infants with Noonan syndrome.  9/70 (12.8%) had bleeding complications in those without comprehensive preoperative testing and undergoing major or dental surgery. Hematology evaluation is indicated in these children.

H Christian et al. J Pediatr 2020; 220: 200-6. Using data from the Longitudinal Study of Australian Children with data points at ages 5 (n=4242) and at ages 7 (n=4431).  Key finding: Owning pets was associate with improved emotional health for children: odds of abnormal emotional scores on SDQ questionnaire was OR 0.81, peer problems OR 0.71, and prosocial behavior OR 0.70 compared with non-pet owners. Prosocial behavior was most improved for children without any siblings with OR 0.21.

Updated Outcome Data for Necrotizing Enterocolitis

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A recent systematic review (IH Jones, NJ Hall. J Pediatr 2020; 220: 86-92) provides contemporary outcomes for infants with necrotizing enterocolitis (NEC). The authors analyzed from 38 articles (from 1375 abstracts); the authors excluded data from developing countries. This review included 21,349 infants with any stage of NEC and 7540 with Bell stage 2a+.

Key findings:

  • Overall mortality was 23.5% in all neonates with confirmed NEC (Bell stage 2a+), 34.5% for infants who underwent surgery
  • Mortality rates were higher for extremely low birthweight infants (<1000 g) at 40.5%; the rate was 50.9% for surgical NEC in this cohort
  • Neurodevelopmental disability was reported in only 4 studies and ranged between 24.8% and 61.1% (n=1209)
  • Intestinal failure was reported with an incidence of 15.2% to 35.0% (n=1370)

A limitation with this study is the lack of agreement on definitions/diagnosis for necrotizing enterocolitis and intestinal failure.

My take: This study shows that NEC still carries a high mortality.

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Sandy Springs

COVID-19 Retractions

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Two recent retractions indicate why multiple studies and careful analysis are often necessary to draw definitive conclusions, even from the most respected journals.

  1. NEJM: Retraction: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621.  Link to original article: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19
  2. Lancet: Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis Original study: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Surprised This Was Published: Liver Transplantation in Undocumented Immigrants

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I was keenly interested in a recent study: BP Lee, NA. Terrault. Liver Transplantation in Unauthorized Immigrants in the United States. Hepatology 2020; 71: 1802-12.  Given the potential for causing a political firestorm, I was surprised it was published.

Definitions: “Unauthorized immigrants, also termed illegal aliens in US federal statures are…all foreign-born non-citizens who are not legal residents.”  Since March 2012, UNOS has required transplant centers to record citizenship…”primarily to better understand transplant tourism.” The authors excluded international transplant tourists in their cohort.

Key findings: 

  • 116 of 43,192 (0.4%) liver transplant (LT) recipients were unauthorized immigrants
  • The majority were from Mexico (52%).  Others came from Guatemala (7%), China (6%), El Salvador (5%) and India (5%).
  • Unauthorized immigrant recipients had a similar risk of graft failure (sHR 0.74) and death (sHR 0.68), though at time of LT, there was higher disease severity (higher MELD scores and increased need for renal replacement therapy).
  • Most LTs for unauthorized immigrants took place in California (47%) and New York (18%).  Texas (3%) and Florida (4%) had a lower proportion of LTs for unauthorized immigrants based on population distribution.
  • The authors note that unauthorized immigrants are different that transplant tourists  –they pay social security tax/other taxes and contribute to organ donation (~3% of donated organs) whereas transplant tourists do not.
  • The authors note that unauthorized immigrant LTs were less than half the number of transplant tourist LTs; the later LT recipients are commonly individuals from Persian Gulf countries.
  • Current federal law mandates that LT be distributed based on “established medical criteria” which does not suggest a “tiered allocation system by citizenship.”  Almost half of the unauthorized immigrant LTs were covered by Medicaid.

My take: Unauthorized immigrants are underrepresented as LT recipients compared to their total population distribution in the U.S.  This likely is due to a number of barriers.  Interestingly, this population is not underrepresented when it comes to organ donation.