Tag Archives: Crohn’s disease

Fiber Intake and Crohn’s Disease

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There are several lines of evidence that diet can contribute to the development and treatment of Crohn’s disease.

From a treatment standpoint, the most dramatic data has been with the effectiveness of enteral nutrition as a treatment option.  In addition other environmental factors like being raised on a farm and use of antibiotics have been shown to alter the risk for Crohn’s disease; the former has been associated with a reduction in risk and the latter with an increased risk.

A new prospective study from 170,776 women followed over 26 years in the Nurses’ Health Study has identified up to a 40% reduction in the risk of Crohn’s disease among the highest fiber intake quintile (24 g/day) in comparison to the lowest intake quintile (12 g/day) (Gastroenterol 2013; 145: 970-77, editorial 925).  Link to abstract: http://dx.doi.org/10.1053/j.gastro.2013.07.050 …

Specific findings:

  • Fruit intake was associated with greatest risk reduction.  The median daily intake of fiber from fruit in the highest quintile was 6 g/day which is equivalent to 2 fruits (eg. banana or orange).
  • Vegetable intake was not associated with protection from Crohn’s disease.
  • The editorial notes that “reverse causation was addressed by evaluating cumulative exposure and including a 2-4 year lag period.”
  • However, the women in this study may not be representative and fiber intake could be an epiphenomenon.  The women in the highest quintile were also less likely to smoke, use aspirin and have a body mass index <30 kg/m-squared.
  • Fiber intake did not significantly reduce the risk of ulcerative colitis

Bottomline: the “Institute of Medicine recommends that daily fiber consumption should be 14 g of fiber for every 1000 calories.”  Thus, if one were to follow the guidelines by the IOM, all individuals would be consuming enough fiber to potentially reduce their risk of Crohn’s disease by 40%.  Other fiber benefits include improve bowel habits, lowered cholesterol levels, weight loss, and lowered diabetes risk.

Related blog links:

Also, in the past week, I posted a blog regarging Hepatitis C (Wiping out Hepatitis C | gutsandgrowth).  Another helpful review of the emergence of new therapies comes from yesterday’s NPR.  This story also reported that the expected (not yet set) cost of sofusbuvir will be $90,000!  Here’s the link:

http://www.npr.org/blogs/health/2013/12/05/248934833/fda-set-to-approve-hepatitis-drug

 

Family Resource for IBD

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In cooperation with ImproveCareNow, EmpoweredByKids.com, which was started by a group of parents, developed ‘The Book of Hope.’ This book “contains stories of hope and inspiration from parents and patients of Inflammatory Bowel Disease.  These are encouraging stories to let families know someone else has been there too and you are not alone.”

You can download a copy of the IBD Book of Hope here.

I read through the downloaded version.  In my view, the general theme was of perseverance.  Given some of the difficulties shared in the book, this book might be best when someone is hospitalized and/or very sick rather than at the onset of diagnosis.

What do you think?

Additional family resource:

Free Self Management Handbook endorsed by ImproveCareNow:

https://improvecarenow.org/patients/self-management-handbook

Related Blog Posts:

IBD References 10/13

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Recent useful references:

Inflamm Bowel Dis 2013; 19: 2490-2500.  “Endemic Fungal Infections in Inflammatory Bowel Disease Associated with Anti-TNF Antibody Therapy”

  • Reviews histoplasmosis, blastomycosis, & coccidioidomycosis. Provides endemic maps (which are available at CDC website), diagnostic tips, and treatment recommendations.  Of these three infections, blastomycosis is endemic in Northern Georgia.
  • Histoplasmosis can be diagnosed with urinary antigen, Blastomycosis is most commonly diagnosed with sputum cultures or bronchial washings for cytology, and coccidioidomycosis can be identified with serology (Coccidioides immittis)
  • Generally a good idea to get a chest radiograph in patients with respiratory symptoms, fever, chills, myalgias, and headaches.
  • CDC Fact Sheet – Centers for Disease Control and Prevention  Map for several endemic fungal diseases, including histoplasmosis and blastomycosis.
  • CDC Features – Valley Fever: Awareness is Key Map for endemic coccidiomycosis.

Inflamm Bowel Dis 2013; 19: 2457-2463. “Efficacy and Safety of Natalizumab in Crohn’s Disease Patients Treated at 6 Boston Academic Hospitals”

  • 44 of 64 with adequate evaluation had either a partial or complete clinical response.  In this select group of complicated patients, about one-third had clinical improvement for more than a year.
  • No cases of PML noted in this cohort.

Inflamm Bowel Dis 2013; 19: 2433-2439. “Serum IL-17A in Newly Diagnosed Treatment-Naive Patients with Ulcerative Colitis Reflects Clinical Disease Severity and Predicts the Course of Disease”

  • Mucosal mRNA expression of IL-17A was 99.8 times higher in ulcerative colitis patients compared to controls.
  • Serum IL-17A correlated with clinical disease severity and was a marker for disease course over the following 3 years.

Inflamm Bowel Dis 2013; 19: 2440-2443. “Assessment of the Relationship Between Quality of Sleep and Disease Activity in Inflammatory Bowel Disease Patients”

  • Data found an association between poor sleep quality and disease activity.  Furthermore, patients in clinical remission with abnormal sleep have a high likelihood of subclinical disease activity (another question for the EPIC smartform?).

Inflamm Bowel Dis 2013; 19: 2423-2432. “Nationwide Temporal Trends in Incidence of Hospitalization and Surgical Intestinal Resection in Pediatric Inflammatory Bowel Diseases in the United States from 1997-2009”

  • Annual percent increase (API) of 2.1% noted in incidence of intestinal resection for Crohn’s disease.  Stable colectomy rate for ulcerative colitis during this period.
  • Annual incidence of hospitalization was 5.7 per 100,000 for Crohn’s and 3.5 per 100,000 for ulcerative colitis; there was a significant increases during study period: 3.8% API for Crohn’s and 4.5% for ulcerative colitis.

Top Lecture: Enteral Nutrition for Crohn’s Disease

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In my opinion, the best lecture from this year’s postgraduate course was from Dr. Baldassano.  Enteral nutrition in Crohn disease: Where should this be in our treatment algorithm?  Robert N. Baldassano, MD (page 115)

Dr. Baldassono has personal experience with improving with enteral therapy after failing methotrexate/remicade.  His conclusion:

Enteral Nutritional Therapy: Where should this be in our treatment algorithm?

  • Should be offered to all newly diagnosed Crohn’s patients who can tolerate Nutritional Therapy
  • Special groups (especially a good idea): Malnourished patients, Younger patients, Growth failure, History of Cancer, Family history of Lymphoma, Consider when failing other therapies

This conclusion is supported by his presentation.

Should we be immunosuppressing our Patients?  Hypothesis: IBD arises from inappropriate handling of intestinal bacteria

Elements of Modern Lifestyle Lead to Changes in Gut Microbiota

  1. Improved sanitation
  2. Less crowded living conditions
  3. Decline in parasites
  4. Vaccinations
  5. Increased antibiotic use
  6. Caesarean section
  7. Refrigeration
  8. Food processing
  9. Diet changes
  10. Improved sanitation

Diet is associated with new onset IBD

  • High dietary intakes of total fats, PUFAs, omega‐6 and meat were associated with an increased risk of CD and UC
  • High fiber and fruit intakes were associated with decreased CD risk
  • High vegetable intake was associated with decreased UC risk.  Reference: Hou JK et al. American Journal of Gastro 2011; 106:563-73
  • The Bacteroides enterotype highly associated with animal protein and saturated fats which suggests meat consumption as in a Western diet
  • The Prevotella enterotype, high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet, more typical of agrarian societies.  References: Wu G, et al. Science. 2011 Oct 7;334(6052):105‐8

Partial or Complete Enteral Nutrition?

  • 50% vs 100% of total caloric needs for induction with elemental formula (PCDAI < 10 at 6 weeks)
  • 50% of total caloric needs 15% remission
  • 100% of total caloric needs 42% remission
  • Labs improved only in the 100% group
  • Weight gain similar in the 2 groups. References: Akobeng et al Clin Nutr 2007; Ludvigsson et al Acta Paediatr 2004;Johnson et al Gut 2006;Critch et al. JPGN: 2012 

Pediatric Longitudinal Study of Semi‐Elemental Diet and Stool Microbiome (PLEASE)

Prospective cohort study of children with Crohn disease from Philadelphia (used Peptamen), Toronto (used Modulen) and Halifax (used Osmolite); (n=90)

  • Enteral therapy with defined formula diet (n=38) vs. anti‐TNFα therapy (n=52)
  • Similar drop in PCDAI and calprotectin in TNF group and diet group. 

Other points:

  1. Insurance generally will cover nasogastric feeds
  2. Disease location –not clear that this matters with Crohn’s disease
  3. The reason EN works may be not what you are giving the patient but what the patient is not getting
  4. Bacterial populations in pediatric IBD subjects on semi‐elemental diet (16S rDNA sequencing) develop a rapid change in gut bacterial populations upon initiating diet.
  5. Partial (50%) nutrition, as noted above, helped maintain remission compared to normal diet.

Nutrition Therapy: “European” Protocol

• Induction:  Exclusive enteral nutrition with an elemental, semielemental,or polymeric formula

• Duration: 4 – 12 weeks

• Maintenance Therapy: (either)

– Nutritional therapy: Repeat 4 week cycle of exclusive enteral nutrition every 3– 4 months

OR

– Medical therapy: 6‐MP/AZA/MTX after induction with nutritional therapy

CHOP EN Experience: What if >80% of calories is from Enteral Nutrition?

  • Methods: Semi‐elemental formula, 80%‐90% of patient’s caloric needs from formula, Nocturnal NG feeds (outpatient teaching program), Normal diet as tolerated during the day
  • Duration:  7 days per week for 8‐12 weeks (induction), 5 days per week (maintenance) Reference: Gupta et al. Inflamm Bowel Dis. 2013:1374-8.
  • Induction of remission: 65% (at 8 weeks)
  • Response: 87% (at 8 weeks)
  • Significant improvement in weight and linear growth
  • Protocol is well tolerated:  no serious adverse events

Postgraduate Course Syllabus (posted with permission): PG Syllabus

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

Crohn’s Research: Going to Pot

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A recent pilot study using Cannabis for Crohn’s disease is certain to attract a lot of attention (Clin Gastroenterol Hepatol 2013; 11: 1276-80).  The side effects are definitely less frightening than many of the accepted treatments.

Background: Cannabis has a long record of medicinal uses; it contains more than 60 different compounds, though Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are thought to be the most active.  Cannabis has known antiinflammatory properties and has been shown to reduce colitis in a mouse model.

Study design/characteristics: 21 of 51 screened patients participated; these patients had active Crohn’s disease despite thiopurines in 20  or 21 and anti-tumor necrosis factor (TNF) therapy in 18.  These 21 patients were enrolled in a double-blind, placebo-controlled study.  The average age in the cannabis group was 46 years compared with 37 in the placebo group.  Both groups received cigarettes twice daily; the cannabis cigarettes had 115 mg of THC whereas the placebo group had cannabis flowers in which the THC had been extracted.  Though this was a double-blind study and efforts were made to mask the psychotropic effects by recruiting patients naive to cannabis, nevertheless, by the end of the study most of the patients knew whether they were in the active group or the placebo group.

Results:

  • Cannabis group had a 45% remission rate (5 of 11) with a CDAI of ≤150; the placebo group had a 10% remission rate.  This did not achieve statistical significance.
  • The response rate (CDAI drop of >100) was noted in 90% (10 of 11) of cannabis group compared with 40% in the placebo group.
  • The mean CDAI reduction was 177 in the study group compared with 66 in the placebo group (P= .005).
  • There were no significant laboratory changes (eg. Hgb, CRP, LFTs, kidney function).
  • No significant side effects were noted.  The study group reported less pain, improved appetite, and better satisfaction with their treatment.

In their discussion, the authors note that this is a small study.  They chose the smoking route with THC-rich cannabis to achieve higher blood levels, but note that oral dosing may be effective.  The 8-week duration of the study and lack of more objective markers of response precludes firm conclusions.

Take-home message: Cannabis should be studied further for its potential role in controlling inflammation.  This study’s timing will increase the broader interest in medical marijuana applications.

Related links:

Thiopurines = Low Efficacy for Crohn’s

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The enthusiasm for thiopurine therapy for Crohn’s disease (CD) had already dropped a lot before two pivotal articles were recently published that confirmed the modest efficacy:

  • Cosnes J, et al. Gastroenterol 2013; 145: 758-65
  • Panes J, et al. Gastroenterol 2013; 145: 766-74
  • Gastroenterol 2013; 145: 714-16 (editorial)

The Cosnes study (from the GETAID group) reports an open-label randomized trial in 147 adult patients with newly diagnosed CD (from 2005–>2010) and risk factors for disabling disease who were recruited from 24 French centers.  Risk factors for disabling disease:

  • Age <40 years
  • Active perianal lesions
  • Corticosteroid use within 3 months of diagnosis

The characteristics and Paris classification are detailed in the paper’s Table 1. Patients were divided into early azathioprine or “conventional” treatment. Patient’s were followed for 3 years.  Azathioprine was dosed at 2.5 mg/kg/day.  The primary endpoint was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission.

Results:

  • 67% of azathioprine group achieved the primary endpoint compared with 56% in the conventional group.  The difference in achieving the primary endpoint was not statistically significant between the two groups.  Also, 41 (61%) of the conventional group were placed on azathioprine (mean time 11 months after enrollment).
  • The azathioprine group patients were more likely to not have perianal surgery (96%) compared with the conventional group patients (82%).
  • Adverse events included pancreatitis in 7 (10%) of azathioprine group compared with 1 (1%) of conventional group.  Elevated liver function tests were noted in 3 (4%) compared with 1 (1%) respectively.  No cases of neutropenia were noted in early azathioprine group.

The latter finding is interesting especially as the authors did not check thiopurine methyltransferase (TPMT) assays in a systematic manner.

Panes et al (for the AZTEC study group) performed a prospective double-blind trial of adult patients with a recent CD diagnosis (<8 weeks).  This study enrolled 131 patients from 31 centers in Spain.  68 received azathioprine (2.5 mg/kg/day) and 63 received placebo.

Results:

  • After 76 weeks of treatment, 30 (44.1%) azathioprine patients and 23 (36.5%) placebo-treated patients were in sustained corticosteroid-free remission (P= .48).
  • Relapse rates were lower in azathioprine group compared with placebo: 11.8% vs 30.2%.
  • Serious adverse effects were more frequent in the azathioprine group compared with placebo: 20.6% vs. 11.1% (P= .16).  In the azathioprine group, 7 (10%) developed pancreatitis, 16 (24%) developed leukopenia, 9 (13%) developed anemia, and 9 (13%) developed abnormal liver function tests.  Infections were more common in the placebo-treated group (24%) compared with 12% in the azathioprine group

The accompanying editorial should be mandatory reading for all health care providers who help manage inflammatory bowel disease (IBD) patients.  The editorial traces how thiopurines (azathioprine and 6-mercaptopurine) became an accepted cornerstone of IBD treatment.  In adults, after initial disappointing results from Summers et al (Gastroenterol 1979; 77: 847-69), efficacy was demonstrated in a seminal study by Present et al (NEJM 1980; 302: 981-87).  However, the authors note that a recent Cochrane review reported that “thiopurines are not effective for induction of remission, but are effective for maintenance of remission.”

The editorial notes that a high degree of efficacy was demonstrated from a small but influential pediatric study of 55 patients.  After a high remission rate (89%) for all patients, this study showed that among those in remission, “1 patient (4%) in the 6MP group had a relapse within 180 days of achieving remission, compared with 7 patients (28%) in the placebo group.”

The editorial draws the following conclusions from the current studies:

  • “The remaining indications for primary therapy with thiopurines are maintenance of steroid-induced remission/steroid sparing in patients with CD that is not newly diagnosed, and prevention of postoperative recurrence.”
  • “The strongest indication for thiopurines may be as part of combination therapy.”
  • “If TNF antagonists had a similar low cost as generic thiopurines, there would likely be little debate regarding an evolution toward treatment of CD with TNF antagonists, either as monotherapy or ideally as combination therapy.  Currently, the annual costs of TNF antagonists is 10-20 times that of thiopurines.”
  • Because of the difference in cost.., “the use of thiopurines in CD is likely to persist, despite the shrinking number of indications, the modest effect size, and the suboptimal safety profile.”

Related blog posts:

Practical Advice on Enteral Nutrition

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In a previous post (NASPGHAN: Enteral Nutrition for Crohn’s Remission | gutsandgrowth), this blog provided a link to NASPGHAN information on enteral nutrition. Having reviewed this information further, I wanted to post some more information about one of the references which offers a terrific professional-quality 32 minute video (from IWK Health Centre in Canada).  This You-tube video on tube feeds provides interviews mostly from kids/family members along with some input by physicians and nutritionists; it is a fabulous resource for families weighing the option of tube feeds.  Around minute 23, a teen walks through the process of NG placement including advice on taping.  Around minute 31, a number of written tips are given like cleaning tubing with vinegar (& then rinsing with water).  According to the website there were only 275 views when I had clicked on this.  If that is accurate, it is a real shame.

Here’s the link:

Crohn’s Survival Guide: The Real Deal on Tube Feeds – YouTube

Other information from the NASPGHAN handout (which offers CME) in the link above:

  • Duration of enteral nutrition to induce remission: 8-12 weeks.  Enteral nutrition can induce remission in about 80% and is similar in effectiveness as corticosteroids.
  • Caloric needs: typically 120% of recommended daily allowance
  • Other foods? usually allowed water or clears like sodas, soup broth, and popsicles.  In some studies, up to 10% of energy intake as various other foods have been allowed; however, this creates a lot of difficulty monitoring.
  • Maintenance strategies: partial enteral nutrition (nighttime feeds only) can reduce recurrence.  More typical approaches included maintenance medication for long-term treatment, or enteral therapy in combination with maintenance medical therapy.  Alternatively, maintenance treatment can be instituted with cycles of 1 month exclusive enteral nutrition every few months.
  • What type of formula for NG tube? most commonly polymeric formulas
  • Refeeding syndrome: in children with severe malnutrition institution of tube feedings should be instituted more slowly over several days with electrolyte monitoring.

Coming Soon to a Pharmacy Near You (part 2)…

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While yesterday’s post reviewed the data that indicate that vedolizumab is likely to be helpful for ulcerative colitis, only small improvements were noted for patients with Crohn’s disease (NEJM 2013; 369: 711-21, GEMINI 2 studies).

Vedolizumab, “a humanized immunoglobulin G1 monoclonal antibody to α4β7 integrin, modulates gut, but not brain, lymphocyte trafficking.”  The GEMINI 2 studies for Crohn’s disease were similar to the GEMINI 1 studies for UC.  However, even more medical centers (n=285) in more countries (n=39) and more patients (n=1115 with 967 receiving study drug) participated.

Baseline characteristics:

  • Median age: 36.1 years
  • Current Smokers: 26.7%
  • Disease location: 16.2% ileum only, 28.3% colon only, 55.4% ileum/colon
  • Median fecal calprotectin: 686 mcg/gram
  • Concomitant medications: 34.2% steroids only, 16.2% immunosuppressives only, 17% both steroids and immunosuppressives, 32.6% neither steroids or immunosuppressives
  • Median steroid dosage: 20 mg
  • Prior TNF antagonist ≥1:  61.8%
  • Prior surgery for Crohn’s disease: 41.8%
  • Prior fistulizing disease: 36.8%

Results:

  • At week 6, 14.5% of vedolizumab-treated patients and 6.8% of placebo-treated patients were in clinical remission (CDAI ≤150).
  • At week 6, 31.4% of study drug group and 25.7% of placebo group had a CDAI-100 response (≥ 100 point decrease in CDAI score).
  • Among patients with an induction response, 39% and 36.4% of vedolizumab every 8 weeks and every 4 weeks, respectively were in clinical remission at week 52, compared with 21.6% of patients assigned to placebo.
  • Vedolizumab-treated patients had increased serious adverse effects including serious infections.  Nasopharyngitis occurred more frequently.
  • Five deaths were noted during the study, four among the treatment group (Crohn’s/sepsis, intentional overdose, myocarditis, and septic shock).
  • No PML cases have been reported among the 3000 patients exposed to vedolizumab

While the response rate to vedolizumab was modest in Crohn’s disease patients, there are some factors that need to be considered in interpreting this data. Unlike in many trials (According to the study which you would never … – gutsandgrowth), this trial included patients with more disease severity.  The authors note that the effects of anti-integrin therapy could be relatively slower acting in Crohn’s disease due to the transmural nature of the disease.  An alternative explanation would be that the gut-selective targeting by vedolizumab is ineffective in most patients with Crohn’s disease due to the need for a more systemic inhibition with transmural disease.

Bottom-line: Among the small percentage of patients who have a response to vedolizumab at week 6, the rates of clinical remission at week 52 were significantly higher than those who received placebo.

Probiotics for Crohn’s Disease –No Beneficial Effects Noted

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With all the buzz regarding how a patient’s microbiome seems to affect everything from metabolic syndrome and colic to autoimmune diseases and inflammatory bowel disease, more attention has been paid in attempts to alter the microbiome for therapeutic benefits.  In Crohn’s disease (CD), the fact that antibiotics have shown beneficial effects have led to a number of studies of probiotics.  A recent study, like previous ones, did not demostrate any benefit with Saccharomyces boulardii (Clin Gastroenterol Hepatol 2013; 11: 982-87).

In this prospective double-blind, placebo-controlled study of 165 patients who achieved remission after steroids or salicylates, subjects were randomly assigned to groups given S boulardii (1 gram per day) or placebo for 52 weeks.

Results:

  • CD relapse occurred in 80 patients: 38 (47.5%) in the probiotic group  and 42 (53.2%) in the placebo group
  • Time to relapse did not differ significantly: 40.7 weeks in probiotic group vs 39 weeks in placebo group
  • No differences were seen in disease activity scores or serum inflammatory markers
  • In post hoc analysis, nonsmokers given S boulardii were less likely to experience a relapse compared with nonsmoker control patients (34.5 % vs. 72%)

One important limitation of this study was not examining the effects of the probiotic on the microbiome of these patients.  Perhaps, other probiotics would be more effective in restoring a “healthy” flora.

Based on these results, and others, the accompanying editorial (pg 988-89), advocates use of probiotics only for prevention of antibiotic-associated diarrhea, prevention of recurrent Clostridium difficile, and treatment/prevention of pouchitis.

Bottom-line: Probiotics have not been demonstrated to be helpful for Crohn’s disease.

Related blog posts:

NASPGHAN: Enteral Nutrition for Crohn’s Remission

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A new document from NASPGHAN highlights the potential for enteric formulas (oral and nasogastric) as an alternative 1st line therapy for Crohn’s disease remission.  The following is a link with specific case examples along with background information and practical advice:

http://goo.gl/p19o0z 

Related blog post:

Rest easy with enteral nutrition | gutsandgrowth