IBD Updates: Rising Burden of IBD, Calprotectin in Severe Colitis, Postoperative Therapeutic Drug Monitoring, Formula Choice for EEN

M Agrawal et al. Gastroenterol 2022; 163: 1547-1554. Open Access! The Rising Burden of Inflammatory Bowel Disease in Denmark Over Two Decades: A Nationwide Cohort Study

Key findings:

  • Between 1995 and 2016, the incidence rate (95% confidence interval) per 100,000 person-years rose from 9.1 (8.3–10.0) to 17.8 (16.8–19.0) for CD, and from 21.0 (19.8–22.3) to 28.4 (27.0–29.8) for UC.
  • The highest increase in CD and UC incidence rates occurred in children and young adults, respectively.
  • The prevalence of IBD doubled from 1995 to 2016; the greatest increase (2.5-fold) was in UC prevalence among individuals aged >40 years. During this period, the median age of the IBD population increased by 6 to 7 years.

Y Pan et al. Inflamm Bowel Dis 2022; 28: 1865-1871. Utility of Therapeutic Drug Monitoring for Tumor Necrosis Factor Antagonists and Ustekinumab in Postoperative Crohn’s Disease

In this retrospective study (n=130), therapeutic drug levels in the postoperative period were associated with improved outcomes for anti-TNF agents (infliximab (IFX) or adalimumab (ADA) but NOT for ustekinumab (UST):

  • In patients with IFX ≥3 µg/mL, higher rates of deep remission (39% vs 0%; P = .02) existed compared with those with IFX less than 3 µg/mL. This was true for clinical remission (44% vs 9%; P = .04) and objective (83% vs 62%; P = .1) remission. 
  •  In patients with ADA ≥7.5 µg/mL, rates of deep (42% vs 0%; P = .02), clinical (42% vs 0%; P = .02), and objective (88% vs 40%; P = .007) remission were higher than patients with lower concentrations.
  • For UST, rates of deep (28% vs 17%; P = 1.0), clinical (33% vs 33%; P = 1.0), and objective (70% vs 67%; P = 1.0) remission were similar between patients regardless of drug concentration.

S Sasidharan et al. Inflamm Bowel Dis 2022; 28: 1833-1837. Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis

In this retrospective study (n=147), a fecal calprotectin >800 mcg/g independently predicted the need for inpatient medical rescue therapy (odds ratio, 2.61; 95% CI, 1.12-6.12). An admission calprotectin >800 mcg/g independently predicted surgery within 3 months (odds ratio, 2.88; 95% CI, 1.01-8.17). My take: This is the least surprising study I’ve read this past month —those with more severe colitis, based on calprotectin values, were more likely to need more intensive treatments.

R Dawson et al. Inflamm Bowel Dis 2022; 28: 1859-1864. Comparing Effectiveness of a Generic Oral Nutritional Supplement With Specialized Formula in the Treatment of Active Pediatric Crohn’s Disease

In this retrospective pediatric study (n=171), the authors found that a generic oral supplement (Fortsip) was as effective as a specialized formula (Modulen IBD) for enteral nutrition. “No difference was demonstrated in remission rate (Fortisip n = 67 of 106 [63%] vs Modulen IBD n = 41 of 64 [64%], P = .89), nonadherence rate (Fortisip n = 7 of 106 [7%] vs Modulen IBD 3 of 64 [5%], P = .57) or method of administration.” The main difference in outcome was a lower expense in the group receiving the generic formula. My take: This study is in agreement with previous studies.

Related blog posts:

Outcomes with Enteral Nutrition

Notice: At this time, gutsandgrowth intends to post blogs 2-3 times per week rather than daily.

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N Davidson et al. JPGN 2022; 75: 70-75. 6- and 12-Month Outcomes after 90:10 Enteral Nutrition Induction Therapy in Pediatric Crohn’s Disease

In this retrospective study (2013-2018), the authors examined outcomes in 105 children treated with a 90:10 enteral feeds (90% formula).

Key findings:

  • 44/105 (42%) patients completed 8–12 weeks
  • After induction, 18 continued EN maintenance with a 80:20 then 70:30 protocol; however, only 10 remained on EN at 6 months and 4 remained on EN at 12 months

The associated editorial (pg: 1-2) make several points:

  1. While EEN is effective and safe, this study and others have shown poor adherence
  2. It is unclear how exclusive enteral nutrition needs to be in order to be effective. And, many patients instructed to receive 90% of their calories as formula are likely consuming higher amounts of table foods
  3. We still are working out which foods need to be excluded

My take: This study shows that EEN is NOT a practical option for most patients beyond induction. Only 4 patients remained on EEN at 12 months.

Related blog posts:

EEN: It Only Works If You Do It

S Mckirdy et al. JPGN 2022; 74: 801-804. The Impact of Compliance During Exclusive Enteral Nutrition on Faecal Calprotectin in Children With Crohn Disease

The expression ‘90% of Success is Showing Up’ has been attributed to Woody Allen. With dietary and medical treatments, adherence is the equivalent of showing up.

In this study, the authors measured fecal gluten immunogenic peptides (GIP), a biomarker of gluten intake, in 45 children (3– 17 years) with Crohn’s disease to assess adherence to enteral nutrition. This, in turn, was correlated with fecal calprotectin (FC) levels.

Key findings:

  • FC decreased in patients with undetectable GIP at both 33 and 54 days of EEN (mean decrease, 33 days: −743 mg/kg, 54 days: –1043 mg/kg, P< 0.001) but not in patients who had detectable GIP levels
  • At EEN completion, patients with undetectable GIP had a lower FC by 717 mg/kg compared with patients with a positive GIP result (P = 0.042) and demonstrated a greater decline from baseline FC (–69% vs +5%, P = 0.011)
  • 13% and 23% had detectable GIP levels at 33 days and 54 days respectively. It is noted that GIP levels are only indicative of short-term consumption (eg. prior 1-2 days) of gluten-containing foods

My take: Dietary therapies are really difficult for most people. This study shows that those with poor compliance are unlikely to benefit.

Related blog posts:

Related blog post: Why I No Longer Need to Be A Billionaire

NASPGHAN 2021 Nutrition Highlights

Thanks to Kipp Ellsworth for forwarding this link:

Nutrition for IBD website: NASPGHAN 2021 Nutritional Highlights

On this website: “Four presentations/lectures were released at the Nutritional Therapy for IBD Virtual Booth that provide a comprehensive review and update of the latest information regarding the use of EEN and therapeutic diets in the management of IBD”

Why Do We Need Dietary Therapies for IBD

Presenter: Lindsey Albenberg, DO

Dr. Lindsey Albenberg, a clinician and researcher from Children’s Hospital of Philadelphia, describes the rapidly increasing incidence of IBD and its relationship to diet, microbiome and the immune system. She reviews the rationale and science supporting the use of dietary therapy to compliment drug therapy as an avenue to potentially achieve higher, more sustainable and possibly safer levels of remission long term in pediatric patients.

The Crohn’s Disease Exclusion Diet Updates: December 2021

Presenter: Rotem Sigall Boneh, RD. Rotem Sigall Boneh, RD, a primary researcher and developer of CDED, provides an overview of the accumulating data with CDED in combination with PEN, including the newly published results of adult data with important endoscopic findings and further shares real world experience and application of nutritional therapy.

IBD Anti-inflammatory Diet or IBD-AID: Proof of Concept

Presenter Ana Maldonado-Contreras, MSc, PhD. Dr. Ana Maldonado-Contreras, a lead researcher in IBD-AID explains the relationship between diet, microbiome and immune function with the design and rational of IBD-AID to manipulate the microbiome. She shares the recently published data of the impact of IBD-AID on the microbiome and cytokine levels specific to food components.

Nutritional Therapy: Perioperative + Complicated Crohn’s Disease

Presenter Andrew S. Day, MB, ChB, MD, FRACP, AGAF

At the NTforIBD Nutritional Symposium prepared for NASPGHAN2021, Professor Day provides insight into the important role of EEN, an underutilized option to both induce remission and improve outcomes in complicated and peri-operative patients.

Dietary Therapy for Adults with Crohn’s Disease

H Yanai et al. The Lancet 2021; The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial https://doi.org/10.1016/S2468-1253(21)00299-5

In this open-label trial of adults with mild-to-moderate biologic naive Crohn’s disease, key findings:

  • At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618)
  • Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group)
  • 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group)

My take: Dietary therapy may be effective option for motivated adult patients with Crohn’s disease.

Related blog posts:

Trial by Diet Approach for Crohn’s Disease in Children

RS Boneh et al. Clin Gastroenterol Hepato 2021; 19: 752-759. Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn’s Disease

The authors collected  data from a multicenter randomized trial of the CD exclusion diet (CDED) in children (mean age, 14.2 ± 2.7 y) with Crohn’s disease who were randomly assigned to groups given either exclusive enteral nutrition (EEN, n = 34) or the CDED with 50% (partial) enteral nutrition (PEN) (n = 39). 

The CDED has been discussed previously on this blog; it aims to avoid animal and saturated fat, milk fat, gluten, specific emulsifiers, taurine, red (reduced heme) and processed meat, and certain fibers from some fruits and vegetables. In addition to excluding patients who received competing therapies (eg. steroids, immunomodulators, and biologics), the authors excluded patients with isolated large bowel disease (L2).

Key findings:

  • At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a dietary response or remission. Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P < .001)
  • Among the 49 patients in remission at week 6, 46 patients (94%) had had a diet response or remission by week 3 and 81% were in clinical remission by week 3

The authors note that the rapid response to dietary therapy suggests a role for a ‘trial by diet’. As such, dietary therapy could be used as monotherapy, for patients failing other therapies, or as a bridge to biological therapy. The authors note that the exact reasons for response to dietary therapy are unsettled and could be “due to both foods excluded and foods enriched in the diet.” In addition, they note that diet appears to be a trigger for inflammation and that reintroduction of foods leads to rebound in inflammation (eg. higher calprotectin) and dysbiosis.

My take: This study shows that dietary therapy works quickly. In this small study, the effectiveness of combined CDED with 50% PEN was similar to EEN.

Related blog posts:

Rhododendrum

Can IBD Be Treated with Diet Alone?

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 Updates: Depression and Crohn’s Disease, Blood Tests in Pediatric IBD

LW Gaines et al. Inflamm Bowel Dis 2020; 26: 423-8. In this study with 3307 adults with Crohn’s disease (CD) and baseline demographics, CD activity and an affective-cognitive index of depression, the authors used structural equation models to determine the likelihood of whether depression triggers CD activity or whether CD activity triggers depression.  Key findings: “The hypothesis that an affective-cognitive depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.”   (Depression is likely to increase CD activity rather than be due to CD activity).

JJ Ashton et al. Inflamm Bowel Dis 2020; 26: 469-76. Among 256 patients (dx 2013-17) in Southhampton-PIBD database, there were 151 with CD, 95 with UC and 10 IBD-unclassified.  Key findings:

  • 9% presented with all normal blood tests (tests analyzed if available: CRP, ESR, Albumin, platelets, packed cell volume, wbc, ALT)
  • Normal labs were more common with UC compared to CD: 14.4% vs 5.3%

RC Ungaro et al. AP&T; 2020; DOI: 10.1111/apt.15685.  (Thanks to Ben Gold for this reference).  Systematic review with meta-analysis: efficacy and safety of early biologic treatment in adult and paediatric patients with Crohn’s disease. A total of 18 471 patients were studied, with  a median follow-up of 64 weeks (range 10-416). Meta-analysis found that early use of biologics was associated with higher rates of clinical remission (OR 2.10 [95% CI: 1.69-2.60], n = 2763, P < 0.00001), lower relapse rates (OR 0.31 [95% CI: 0.14-0.68], n = 596, P = 0.003) and higher mucosal healing rates (OR 2.37 [95% CI: 1.78-3.16], n = 994, P < 0.00001) compared with late/conventional management. Conclusions: Early biologic treatment is associated with improved clinical outcomes in both adult and paediatric CD patients, not only in prospective clinical trials but also in real-world settings.

RS Boneh et al. Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn’s Disease Clin Gastroenterol Hepatol (online April 14, 2020, in press) Thanks to KT Park’s Twitter feed for this reference.

  • Methods: We collected data from the multicenter randomized trial of the CD exclusion diet (CDED). We analyzed data from 73 children with mild to moderate CD (mean age, 14.2±2.7 y) randomly assigned to groups given either exclusive enteral nutrition (EEN, n=34) or the CDED with 50% (partial) enteral nutrition (n=39). Patients were examined at baseline and at weeks 3 and 6 of the diet. Remission was defined as CD activity index scores below 10 and response was defined as a decrease in score of 12.5 points or clinical remission. Inflammation was assessed by measurement of C-reactive protein.
  • Results: At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a dietary remission (DiRe). Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P<.001). Among the 49 patients in remission at week 6, 46 patients (94%) had a DiRe and 81% were in clinical remission by week 3. In multivariable analysis, remission at week 3 increased odds of remission by week 6 (odds ratio, 6.37; 95% CI, 1.6–25; P=.008) whereas poor compliance reduced odds of remission at week 6 (odds ratio, 0.75; 95% CI, 0.012–0.46; P=.006).
  • Conclusions: For pediatric patients with active CD, dietary therapies (CDED and EEN) induce a rapid clinical response (by week 3).

Related blog posts:

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

 

CCFA: Updates in IBD Conference (part 2)

My notes from Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Sandy Kim, MD –Children’s Hospital of Pittsburgh

Diet in Inflammatory Bowel Disease: Food for Thought

This was a terrific lecture –though much of the topic has been reviewed recently in this blog: Dietary Therapy for Inflammatory Bowel Disease.

Key points:

  • Changes in diet can change microbiome quickly, within 24 hrs
  • Some diets (eg. more fruit/vegetables/fish) may help lower risk of developing IBD
  • Dietary therapy, especially exclusive enteral nutrition (EEN), is effective therapy for Crohn’s disease
  • Why does EEN work?  It is not clear.  There are some changes in microbiome but decrease or little change overall in microbial diversity
  • Reviewed newer dietary approaches: SCD (www.nimbal.org), CD-TREAT, Crohn’s Disease Exclusion Diet

Related blog posts:

Frank Farraye, MD –Mayo Clinic

Health Maintenance in the Adult Patient with IBD

  • Good Practice: Update Vaccinations in IBD population
  • Recent concerns include measles outbreak, and frequent occurrence of Herpes zoster
  • No evidence that vaccination exacerbates IBD
  • New Hepatitis B Recombination Vaccine (Heplisa-B) -2 doses given over one month (for patients older than 18 years. Seroprotective anti-HBs after two doses: 95.4%
  • Shingrix -new recombinant Zoster vaccine.  Overall efficacy 97.2%.  Frequent adverse reactions
  • Women with IBD should undergo annual cervical cancer screening
  • IBD patients should be seen by dermatology
  • Consider depression screening in IBD patients
  • Counsel patients to quit smoking
  • Consider bone density screening in at risk patients

One audience member (Jeff Lewis, MD) pointed out that more attention needs to be paid to depression and anxiety which are much more common and more frequently health-threatening than issues like vaccination.

Related blog posts:

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

 

Dietary Therapy for Inflammatory Bowel Disease –Useful Update

Recently, Lindsey Albenberg, DO (from CHOP) provided an excellent update on dietary therapy for Crohn’s disease.  She was an invited speaker from CHOA as part of a nutritional support professional development series.  Thanks to Kipp Ellsworth for coordinating this.

Full Slide Set: Nutritional therapies for IBD

Key points from lecture:

  • At CHOP, exclusive enteral nutrition (EEN) is the main dietary approach for Crohn’s disease (CD) advocated due to better proof of its effectiveness
  • In children, EEN is as effective as steroids for clinical improvement and better in terms of mucosal healing
  • EEN therapy can be given regardless of CD location
  • For EEN, there is no difference in response between elemental and nonelemental formulas
  • For EEN to be effective, at least 80-90% of all calories need to be administered during induction
  • At CHOP, EEN is often administered at time of diagnosis and oral approach is tried first
  • Newer dietary approaches are being studied and may be effective.  Diets like the specific carbohydrate diet (SCD) can be considered, particularly in patients with milder disease.

 

The following slide presents SCD diet studies –mostly small studies except for 2016 survey study.

Related blog posts:

 

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