Can IBD Be Treated with Diet Alone?

Posted on by

This question was debated recently in GI and Hepatology News: Can IBD be treated with diet alone?

Ashwin N. Ananthakrishnan, MD, MPH argues that IBD can be treated with diet alone:

  • “Randomized controlled trials published more than a decade ago demonstrated that exclusive enteral nutrition, wherein all table foods are eliminated from a diet and the patient relies on an elemental diet alone for nutrition, was effective in not just inducing clinical remission but also improving inflammatory biomarkers.”
  • “More recent rigorous studies have demonstrated that the effects of exclusive enteral nutrition can be mimicked either by a selected, less-restrictive diet (such as CD-TREAT4), which is more sustainable, or by combining partial enteral nutrition with an elimination diet that is quite diverse (such as CDED5).”

Laura Raffals, MD, MS argues against treating IBD with dietary therapy.

  • “Exclusive enteral nutrition (EEN) has been studied the most rigorously of all diets in IBD and has demonstrated the greatest benefit, compared with other diet studies in IBD. EEN requires the intake of elemental, semi-elemental, or polymeric formulas to meet all nutritional requirements without additional intake of food for 6-8 weeks. Studies have been performed mostly in pediatric populations and have shown effectiveness in induction of remission with reduction in inflammatory markers, including C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, and even mucosal healing. EEN has not worked out as well for adult populations, because of the poor tolerability of exclusive intake of enteral formulas.”
  • “Beyond EEN, there are many diets that have been considered … only the SCD and Crohn’s disease exclusion diets have shown improvement in clinical remission and reduction in inflammatory markers.”
  • “Most dietary studies are underpowered, lack a control arm, and do not include endoscopic endpoints. The current body of evidence remains insufficient to support the use of diet alone for the treatment of IBD.”

My take: Except for exclusive enteral nutrition (EEN) which is quite challenging, dietary therapies have not been proven as effective long-term stand-alone treatments. In patients who choose dietary therapy, careful monitoring is particularly important.

Related blog posts:

IBD Update -December 2020

Posted on by

DHW Little et al. Am J Gastroenterol 2020;115:1768–1774. Effectiveness of Dose De-escalation of Biologic Therapy in Inflammatory Bowel Disease: A Systematic Review (Thanks to Ben Gold for this reference)

In this systematic review, a total of 995 adult patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial.

Key findings:

  • Biologic dose de-escalation was associated with relapse rates as high as 50% at 1 year. Overall, clinical relapse occurred in 0%–54% of patients who dose de-escalated biologic therapy (17 studies).
  • Lower rates of relapse (10%–25%) were reported in studies involving patients with endoscopic and/or histologic remission
  • These results are in agreement with a previous meta-analysis, which found a 1-year risk of relapse after discontinuation of anti-TNF therapy of 36% in CD and 28% in UC ( Gisbert JP, et al.. Am J Gastroenterol 2016;111:632–47).

My take: This study shows that dose de-escalation of biologic therapy in IBD
seems to be associated with high rates of clinical relapse

C Chapuis-Biron et al. Am J Gastroenterol 2020;115:1812–1820. Ustekinumab for Perianal Crohn’s Disease: The BioLAP Multicenter Study From the GETAID (Thanks to Ben Gold for this reference too)

In this national multicenter retrospective cohort study in 207 adult patients with either active or inactive perianal Crohn’s disease (pCD) who received ustekinumab (2017-2018). The majority had received multiple biologics (~85% had at least 2 anti-TNF agents, 28% had received vedolizumab) and prior anal surgeries (mean 2.8).

Methods: Success of ustekinumab was defined by (i) clinical success at 6 months of treatment assessed by the physicians’ judgment, with (ii) no need for dedicated medical treatment for perianal lesions (antibiotics and/or topics) nor (iii) unscheduled surgical treatment. For perianal disease evaluation, clinical success was defined in the study protocol, by the absence of draining pus for fistulas, and no anal ulcers

Key findings:

  •  In patients with active pCD, success was reached in 57/148 (38.5%) patients.
  • Among patients with setons at initiation, 29/88 (33%) had a successful removal.
  • In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively.
  • The absence of ustekinumab optimization was associated with upper odds of success (OR 2.74). “We can suppose in our present study that optimization of treatment was needed in severe refractory patients with no or insufficient response to ustekinumab. Thus, in these nonresponders, success was not achieved despite optimization.”

My take (partly borrowed from authors): “This large multicenter dedicated study adds
substantial evidence to the growing literature on ustekinumab effectiveness in refractory CD.” For pCD, optimization of ustekinumab has a low likelihood of improving response.

Related blog posts -De-escalation:

Related blog posts -Ustekinumab/Crohn’s Disease:

COVID-19 -Now #1 Cause of Death in U.S.

Posted on by

S Woolf et al. JAMA. Published online December 17, 2020. doi:10.1001/jama.2020.24865: Full text: COVID-19 as the Leading Cause of Death in the United States

  • Between November 1, 2020, and December 13, 2020, the 7-day moving average for daily COVID-19 deaths tripled, from 826 to 2430 deaths per day
  • As occurred in the spring, COVID-19 has become the leading cause of death in the United States (daily mortality rates for heart disease and cancer, which for decades have been the 2 leading causes of death, are approximately 1700 and 1600 deaths per day, respectively)

Related blog posts:

Vaccine Strategy: Nate Silver’s twitter feed suggests that after vaccination of medical personnel, focus of vaccine efforts should rely on age rather than at-risk conditions (which could affect 100 million in U.S). Using an age-based system would also be easier; it would minimize influence and wealth in the distribution of the vaccine.

COVID-19: Excess Mortality in Younger Adults

Posted on by

From NEJM Journal Watch: COVID-19: Excess Mortality in Younger Adults

“Excess mortality in younger adults: Among U.S. adults aged 25 to 44, there were 19% more deaths than expected — or 12,000 people — from March through July 2020. In JAMA, the researchers — including Dr. Rochelle Walensky, who has been nominated to lead the CDC — report that 38% of this excess mortality was directly from COVID-19, but that proportion varied by region. Deaths from COVID-19 were similar to or exceeded unintentional deaths from opioids in this age group in 2018 in several areas of the country. The authors write that this may be an underestimate of the COVID-19 mortality burden in younger adults, as they may have been undertested.”

Link to study: All-Cause Excess Mortality and COVID-19–Related Mortality Among US Adults Aged 25-44 Years, March-July 2020

Bone Health in Children with Biliary Atresia

Posted on by

S Ruuska et al. JPGN 2020; 71: 707-712. Impaired Bone Health in Children With Biliary Atresia

This retrospective study from Finland details the bone health of children with biliary atresia (BA). Key findings:

  • Out of 49 patients, 7 (14%) were diagnosed with rickets during infancy. Clearance of jaundice [odds ratio 0.055, 95% confidence interval [CI] 0.00266–0.393; P < 0.01] was a protective factor against rickets.
  •  In DXA measurements, median lumbar spine aBMD anthropometrically adjusted z-scores were as follows:
    • in native liver survivors 0.8 (interquartile range [IQR] −1.9 to 1.4) at 5 and −0.3 (IQR −1.3 to 0.8) at 10 years
    • in liver transplanted patients 0.4 (IQR −0.2 to 1.1) at 5 and 0.6 (IQR −0.1 to 1.3) at 10 year.
  • Most BA patients have aBMD within normal range between 5 and 10 years of age irrespective of liver transplantation status.

My take: This study shows that early in life there is frequent bone impairment in children with BA. This generally improves in most children as cholestasis resolves (with or without liver transplantation).

Related blog posts:

Indian Rocks Beach, FL

Intestinal Inflammation in Patients with Cystic Fibrosis

Posted on by

An interesting study (C Tetard et al. JPGN 2020; 71: 778-781. Reduced Intestinal Inflammation With Lumacaftor/Ivacaftor in Adolescents With Cystic Fibrosis) describes the association of Lumacaftor/Ivacaftor and improvement in intestinal inflammation based on calprotectin levels.

This was a small study with 15 patients, with 9 patients having very elevated fecal calprotectin (FC) (>250) and the median level was 713 mcg/g for the entire cohort at baseline. After treatment with lumacaftor/Ivacaftor, median FC level was 102 mcg/g.

This pilot study is intriguing and makes the point that intestinal inflammation is commonly seen in children with cystic fibrosis. However, this study has some striking differences from prior studies.

My take: This study suggests that Lumacaftor/Ivacaftor is associated with a significant decrease in intestinal inflammation. When one looks at prior studies, the FC values presented in this study at baseline are much greater which could indicate significant selection bias.

Related blog posts:

Indian Rocks Beach, FL

Normative Data for Fecal Calprotectin, age 4-16 yrs

Posted on by

This study collected prospective data from 212 children. Key finding: The median and 95th percentile for fCP were 18.8 mg/kg and 104.5 mg/kg, respectively. “We found a statistically significant association between the 95th percentile of fCP concentrations and age (p < 0.001).”

My take: This is another study showing that calprotectin cut off values need to be higher in younger children.

Related blog posts:

Is GLP2 Worth $300K per Year?

Posted on by

E Ramos Boluda et al. JPGN 2020; 71: 734-739. Experience With Teduglutide in Pediatric Short Bowel Syndrome: First Real-life Data

S Hill. JPGN 2020; 71: 697-698 (editorial) Use of GLP-2 May Herald a New Era of Improved Outcome of Short Bowel Syndrome-associated Intestinal Failure

The study and associated editorial highlight the effectiveness of GLP-2 in a prospective cohort of 17 patients with short bowel syndrome. It is noted that Dr. Hill has received funding from the pharmaceutical manufacturer of the product.

Key findings:

  •  A total of 12 of 17 patients achieved parenteral independence: 3 patients after 3 months of treatment, 4 patients at 6 months, and 5 after 12 months.
  • The percentage able to wean off parenteral nutrition was 17%, 44%, and 60% at 3, 6, and 12 months respectively. Only 1 patient did not exhibit improvement
  • Plasma citrulline levels, a marker for enteral autonomy, increased from a baseline average of 20 micromol/l to 37.5, 46.75, and37.9at 3, 6, and 12 months respectively.
  • Adverse reactions included abdominal pain 30%, nauseas 18%, injection-site reactions 22%, and headache 16%.

Both the editorial and the study comment briefly on the cost of the therapy. The editorial also notes the current recommendation for surveillance endoscopy in view of a hypothetical risk of malignancy.

My take: Is GLP2 Worth the Cost? It probably depends on who is paying and long-term safety data. Perhaps, we will develop tools to improve prediction of which patients will achieve enteral autonomy with GLP2 who would otherwise require ongoing parenteral nutrition.

Related blog posts:

Treating Pediatric Hepatitis C Infections is Cost-Effective. Plus COVID-19 mRNA Vaccine Study

Posted on by

E Greenaway et al. J Pediatr 2020; DOI:https://doi.org/10.1016/j.jpeds.2020.08.088. Free full text: Treatment of Chronic Hepatitis C in Young Children Reduces Adverse Outcomes and Is Cost-Effective Compared with Deferring Treatment to Adulthood

Methods: A state-transition model of chronic HCV was developed to conduct a cost-effectiveness analysis comparing treatment at age 6 years vs delaying treatment until age 18 years

Key findings:

  • After 20 years, treating 10 000 children early would prevent 330 cases of cirrhosis, 18 cases of hepatocellular carcinoma, and 48 liver-related deaths
  • The incremental cost-effectiveness ratio of early treatment compared to delayed treatment was approximately $12 690/quality-adjusted life-years gained and considered cost-effective

My take (=conclusion from authors): Delaying treatment until age 18 years results in an increased lifetime risk of late-stage liver complications. Early treatment in children is cost effective. Our work supports clinical and health policies that broaden HCV treatment access to young children.

Related blog posts:


FP Polack et al. NEJM Full text link: Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Published data on the Pfizer/BioNTech vaccine

Excess Deaths From COVID-19 and Other Causes

Posted on by

For musical fans: 2020: The Musical YouTube Link (~8 minutes) with Jimmy Fallon and Andrew Rannells

SH Woolf et al.. JAMA 2020; 324: 510-513. Excess Deaths From COVID-19 and Other Causes, March-July 2020

The authors compared deaths from 2014-2020 using data from the National Center for Health Statistics and US Census Bureau.

Key findings:

  • Between March 1 and August 1, 2020, 1 336 561 deaths occurred in the US, a 20% increase over expected deaths (1 111 031 [95% CI, 1 110 364 to 1 111 697]). 
  • Of the 225 530 excess deaths, 150 541 (67%) were attributed to COVID-19
  • The authors conclude that the excess deaths attributed to causes other than COVID-19 could reflect deaths from unrecognized or undocumented infection with severe acute respiratory syndrome coronavirus 2 or deaths among uninfected patients resulting from disruptions produced by the pandemic

My take: The COVID-19 situation has worsened considerably in the past 2 months and the final toll from this infection will be truly staggering; this unfortunately will include its indirect effects due to deferral of care