Predicting Response to Vedolizumab and Ustekinumab for Inflammatory Bowel Disease

Posted on by

A recent review (A Barre, JF Colmbrel, R Ungaro. Alim Pharm Ther 2018 DOI: 10.1111/apt.14550) discusses predictors of response to vedolizumab and ustekinumab for inflammatory bowel disease (IBD). Thanks to Ben Gold for this reference.

Background:

  • “Vedolizumab is a humanised monoclonal gut-selective antibody against α4β7 integrin and inhibits the trafficking of inflammatory cells to the intestine.”
  • From Vedolizumab GEMINI trials, , “primary response to vedolizumab was typically evaluated at week 14 after induction with rates of clinical remission and clinical response ranging between 24%-36% and 49%-64% in CD, and 23%-39% and 43%-57% in UC, respectively”
  • “Ustekinumab is a monoclonal IgG1 antibody against the p40 subunit of interleukin-12 (IL-12) and interleukin-23 (IL-23) that targets both the T-helper 1 and T-helper 17 pathways involved in the pathogenesis of CD.”
  • With Ustekinumab, “in real-world observational studies, patients were treated off-label and received highly variable induction and maintenance dosing, thus limiting the generalizability of results. The rates of response were reported to be as high as 84% and remission rates as high as 35% at end of induction, with loss of response in around one-third of patients during maintenance”

Key points:

  • Patients with severe disease (by clinical activity and inflammatory biomarkers), and prior anti-TNF exposure are less likely to respond to vedolizumab.
  • Ileocolonic disease, no prior surgery and uncomplicated phenotype were associated with better responses to ustekinumab in CD

With ustekinumab, in particular, there is still very limited data on its effectiveness and long-term outcomes and this is even more the case in pediatrics. This review does a good job in compiling the current available data.

My take: While this is a nice review, it does not help me much with developing an algorithm for how I will use these relatively new medications for IBD.

Related blog posts:

Bright Angel Trail

Oats OK in Celiac Disease

Posted on by

A recent double-blind, randomized, placebo-controlled trial (E Lionetti et al. J Pediatr 2018; 194: 116-22) examined the effect of adding oats to the diets of 79 children and compared this to a control group of 98 children; all participants had biopsy-proven celiac disease (CD).

Background:

  • “A large body of evidence has so far suggested that the consumption of pure oats is safe in the vast majority of patients with celiac disease.”
  • Still concerns persist.  In addition, the purity of oats cannot always be guaranteed.
  • Previous studies were limited by small sample sizes, short follow-up, limited details regarding oat used, and lack of detail about cross-contamination.

This study sought to remedy prior trial deficiencies and examined clinical indices,  serology, and intestinal permeability after 6, 9 and 15 months.

Key finding:

  • There were no statistically significant clinical, serologic, or intestinal permeability variables when comparing the oat group to the control group.

My take: Oats, free of cross contaminants, are safe to incorporate into a gluten-free diet for CD.

Canyon Rim

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

The Latest on Pediatric Nonceliac Gluten Sensitivity

Posted on by

 A recent study (R Francavilla et al. Am J Gastroenterol advance online publication, 30 January 2018; doi: 10.1038/ajg.2017.483 ) examined “non-celiac gluten sensitivity” (NCGS) in a multicenter prospective trial from Italy (2013-16). 

This study included 1,114 children with chronic gastrointestinal symptoms and negative for both celiac disease and wheat allergy.  To determine if these children, had  a positive correlation between symptoms and gluten ingestion they were evaluated consecutively through the following phases: run-in, open gluten-free diet (GFD) and DBPC crossover gluten challenge.

Design: If there was a correlation between symptoms and gluten ingestion, then patients were randomized to gluten (10 g/daily) and placebo (rice starch) for 2 weeks each, separated by a washout week. The gluten challenge was considered positive in the presence of a minimum 30% decrease of global visual analogue scale between gluten and placebo.

Key findings:
  • Out of 1,114 children, 96.7% did not exhibit any correlation with gluten ingestion.
  • Among the 36 patients who seemed to show a correlation between gluten ingestion and symptoms, 28 patients entered the DBPC gluten challenge. Of these 28 children, eleven children (39%) tested positive.
  • “No predictive laboratory tests can help in identifying NGCS”

Also, it is worthwhile to quote the authors from their last paragraph: “philosopher Immanuel Kant [said], ‘all our knowledge begins with the senses, proceeds then to understanding, and ends with reason’. NCGS begins in the gut feeling of patients, and we are still in the process of understanding it, hoping that reason is not too far behind.'”

My take: This study shows that very few children (<4%) with chronic gastrointestinal symptoms had correlation with gluten ingestion. Even in this group, NGCS was excluded with a DBPC in >60% of cases.

How Gluten Free is a Gluten-Free Diet?

Posted on by

A recent analysis (JA Syage et al.The American Journal of Clinical Nutrition, Volume 107, Issue 2, 1 February 2018, Pages 201–207, https://doi.org/10.1093/ajcn/nqx049) (Thanks to Kipp Ellsworth for this reference) of 259 patients with celiac disease (~75% pediatric) showed that a large number with ongoing gluten ingestion based on urine and stool tests of gluten excretion.

Results: The average inadvertent exposure to gluten by CD individuals on a GFD was estimated to be ∼150–400 (mean) and ∼100–150 (median) mg/d using the stool test and ∼300–400 (mean) and ∼150 (median) mg/d using the urine test. The analyses of the latiglutenase data for CD individuals with moderate to severe symptoms indicate that patients ingested significantly >200 mg/d of gluten.

My take (borrowed from authors): These surrogate biomarkers of gluten ingestion indicate that many individuals following a GFD regularly consume sufficient gluten to trigger symptoms and perpetuate intestinal histologic damage.

Free link to full article: Determination of gluten consumption in celiac disease patients on a gluten-free diet

Despite signs like these, a lot of individuals veer off the path.

Can Infants Self-Regulate their Feeding and Prevent Obesity?

Posted on by

A terrific summary of a recent prospective study (RW Taylor et al. JAMA Pediatr. 2017;171(9):838-846. doi:10.1001/jamapediatrics.2017.1284): NY Times: What Happens When You Let Babies Feed Themselves?

An excerpt:

Baby-led weaning is an approach to feeding that encourages infants to take control of their eating. It’s based on the premise that infants might be better self-regulators of their food consumption..

A recent randomized controlled trial accomplished what previous work could not. Pregnant women in New Zealand were recruited before they gave birth and randomly assigned to one of two groups…

The study found no significant differences in the children’s body mass indexes at 12 or 24 months. Even when researchers restricted the analyses to the most adherent subjects, there were no significant differences over all in B.M.I…

Nonetheless, there might be merit to giving infants more control over their eating: This study found that baby-led weaning resulted in children who were less fussy about what they ate and who seemed to enjoy their food more…

But if we want to find a larger solution to the issues of overweight American children and obesity, it seems we’re going to have to work harder. Babies aren’t going to solve the problem for us.

My take: This study demonstrates the fallacy of the idea that humans naturally self-regulate the right amount of food intake.

It’s Alimentary (Part 3)

Posted on by

A recent ‘clinical quality forum’ sponsored by The Children’s Care Network (TCCN) and Nutrition4Kids featured several good lectures. The symposium was titled “It’s Alimentary.” What follows are my notes –the full lectures from these talks will be available in the coming weeks on the Nutrition4Kids website. My notes may include some errors in transcription and errors of omission.

“The Importance of Intestinal Microbiota in Pediatric Health and Disease” by W Allan Walker (Harvard Medical School, Director of Division of Nutrition) reviewed data showing how changes in the microbiome, likely related to a ‘Western lifestyle’ has resulted in numerous health consequences.

Key points:

  • The hygiene hypothesis has correlated a greatly reduced risk of infections inversely to an increase in immune-mediated diseases including Crohn’s disease, multiple sclerosis, type 1 diabetes mellitus, and metabolic syndrome/obesity.
  • The consequences of improved hygiene are likely mediated by alterations in gut microbiome
  • To counter alterations in a ‘healthy’ microbiome, perhaps most important is normal neonatal colonization.  This, in turn, is related to healthy pregnancy/full term gestation, vaginal delivery, absence of antibiotics in the first year of life (if feasible), and exclusive breastfeeding.
  • A healthy first-year-of-life microbiome leads to improved tolerance (less allergies) and absence of chronic diseases.
  • In those at risk for altered microbiome, probiotics may be beneficial.
  • By 12-18 months, the microbiome has an ‘adult’ pattern of colonization with a bacterial signature that is present for the rest of someone’s life

Related blog posts:

A subsequent segment addressed “Weight Bias in Healthcare Professionals and What We Can Do About It” by Sheethal Reddy (Strong4Life Clinical Psychologist).

Key points:

  • Physicians have been shown to exhibit decreased empathy with obese patients (KA Gudzune et al. Obesity 2013; 21: 2146-52)
  • Bias can not be eliminated but can be better understood. The Implicit Attitude Test can help ascertain one’s level of bias. https://implicit.harvard.edu/implicit
  • Ways to address obesity as a topic: “Is it OK to talk about…”, use of health report cards to review BMI
  • “The most important thing you can be is kind”

Related blog posts:

In another talk was related to obesity: “ERAS Nutrition in Bariatric Surgery” by Mark Wulkan (Emory University Professor of Surgery). ERAS is an acronym for Enhanced Recovery After Surgery –pioneered in colorectal surgery (Previous post on ERAS: ERAS-Enhanced Recovery after surgery)

Key points:

  • Using ERAS protocol, hospital length of stay has been shortened from 2 days to 1 day
  • ERAS protocol has been associated with minimal use of narcotics –occasionally for breakthrough pain.
  • Current bariatric surgery favored by Strong4Life team –Laparoscopic Sleeve Gastrectomy

Related blog entries:

Bariatric Surgery Candidates

It’s Alimentary (Part 2)

Posted on by

A recent ‘clinical quality forum’ sponsored by The Children’s Care Network (TCCN) and Nutrition4Kids featured several good lectures. The symposium was titled, “It’s Alimentary.” What follows are my notes –the full lectures from these talks will be available in the coming weeks on the Nutrition4Kids website. My notes may include some errors in transcription and errors of omission.

In my view the best lecture from this symposium was given by Kathleen Zelman (WebMD, Director of Nutrition): Diet and Nutrition Trends Impacting Health

Key points:

  • There have been more individuals pursuing vegetarian and vegan diets.  Though increasing vegetables/fruits is a good trend, vegan diets are particularly challenging (& potentially dangerous) in children.  In those who take milk and eggs, this diet is much more likely to meet nutrient needs.  These diets necessitate the assistance of a dietician.
  • Unfavorable trends: increased consumption of highly processed foods and restrictive food fads.  Some processed foods (eg. canned beans) can be a healthy addition to diet.
  • ‘Organic diets are not more nutritious. They are great if you can afford it. Key is eating more vegetables and fruits.’
  • GMOs are safe.
  • MyPlate.gov is a good resource
  • Encourage families to eat together and to shop for a ‘rainbow of colors’

Related posts:

A subsequent lecture on “Nutrition for the Premature Infant” by Heidi Karpen (Emory University, Professor of Pediatrics) provided a good overview of the ongoing efforts to improve nutritional outcomes for premature infants.

Key points:

  • Good nutrition is crucial for better neurodevelopmental outcomes and stronger bones.
  • Despite efforts like instituting TPN on first day of life, most neonates are losing ground during their hospitalization.
  • Breastmilk is best at reducing sepsis, necrotizing enterocoliitis, and improving IQ.  However, it is not perfect  –less protein, less calcium, and less phosphorus than formulas; thus, breastmilk needs to be augmented and/or supplemented.
  • Informal breastmilk donation can be dangerous.  Donor breastmilk needs to be carefully screened.

Related blog posts:

 

It’s Alimentary (Part 1)

Posted on by

A recent ‘clinical quality forum’ sponsored by The Children’s Care Network (TCCN) and Nutrition4Kids featured several good lectures. The symposium was titled, “It’s Alimentary.”  What follows are my notes –the full lectures from these talks will be available in the coming weeks on the Nutrition4Kids website. My notes may include some errors in transcription and errors of omission.

“The Fiber Movement: Why Kids Need It and How to Get It” by Maria Oliva-Hemker (Director of Division of Pediatric Gastroenterology, Johns Hopkins). This was a terrific lecture which pulled together a lot of useful information.   Despite hearing a lot about fiber, this lecture showed me that there is a lot that I still need to learn.

Key points:

  • Institute of Medicine recommends 14 grams of fiber per 1000 kcal of dietary intake.  This is a higher amount of fiber than prior recommendations.
  • Most adults are consuming about 50% of the fiber that they should
  • Whole foods should be encouraged over fiber supplements
  • Increased fiber associated with lower risk of obesity, stroke, coronary heart disease, and diabetes

Related blog posts:

“The LEAP Study and Its Implication for the Future of Food Allergies” Kiran Patel (Professor Pediatrics, Division of Allergy and Immunology, Emory University)  This was the second opportunity that I had to hear Dr. Patel in the past 6 months –see An Allergy-Immunology Perspective on GI Diseases

Key points:

  • There has been an increasing incidence of peanut allergies
  • Early introduction of peanuts helps reduce peanut allergies. Suggested algorithm
  • To reduce allergies, placing a best practice alert in electronic record could be necessary as rates of encouraging early peanut introduction in at risk children remains low

Related blog posts:

 

LEAP study results

Slides with information on introduction of peanuts –this should be discussed with physician before implementation.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

Choosing the Right Intravenous Fluids

Posted on by

A recent “SALT-ED” study (WH Self et al. NEJM 2018; 378: 819-28) with more than 13,000 noncritically-ill adults indicated that patients who received normal saline had increased incidence of major adverse kidney events compared to those who received more balanced fluids like lactated Ringers’ or Plasma-Lyte A.

A 2 min quick take summary:Comparison of Crystalloids and Saline for Noncritically Ill

In a separate “SMART” study (MW Semler et al. NEJM 2018; 378: 829-39), investigators looked at balanced crystalloids versus saline in critically-ill adults (n=15,802).  The use of balanced crystalloids (compared to saline) resulted in a lower rate of mortality (10.3% vs 11.1%, P=.06) and fewer major adverse kidney events (14.3% vs. 15.4%, P=.04).