Tag Archives: Crohn’s disease

Ups (mostly) and Downs with IBD Epidemiology

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Two articles describe both increasing and decreasing trends in the prevalence of inflammatory bowel disease (IBD).

  • Y Ye et al. Inflamm Bowel Dis 2020; 26: 619-25, editorial 626-27
  • M Torabi et al. Inflamm Bowel Dis 2020; 26: 581-90, editorial 591-92 

The first study by Ye et al provides the familiar message that IBD prevalence has been increasing in pediatrics and adults.  This study examined 2 large claims databases.  The Optum database covered ~18 million annually during the study period (total ~57 million from 2007-2017) and Truven covered ~44 million annually (total ~240 million since 1995)

Key findings:

  • Pediatric IBD prevalence increased by 133% from 2007 to 2016: from 33 per 100,000 to 77 per 100,000. Crohn’s disease (CD) was twice as prevalent as ulcerative colitis (UC) in the pediatric population (46 vs 22)
  • Adult IBD prevalence increased by 123% from 2007 to 2016: from 215 per 100,000 to 478 per 100,000. The prevalence rates of CD and UC were similar in adults: 198 vs 181)
  • The Northeast region had the highest prevalence of IBD, followed by Midwest, South and then West.
  • Based on these prevalence data, there are an estimated 58,000 children (2-17) and 1.2 million adults with IBD in U.S.   Or, 1 in 1299 children and 1 in 209 adults.

Limitations:

  • Diagnosis and data derived from claims database
  • Cases can vary significantly based on how sensitive the definition for IBD is in a given study.  In this study, the authors indicate in supplementary material, that the prevalence rates could be doubled in adults if they chose a more sensitive/less specific case definitions.

The second study by Torabi et al, which utilized the Manitoba Epidemiology Database (n=1.2 million) showed a decrease in IBD incidence.  The authors examined 296 small geographic areas (SGAs) and found that many had persistently high IBD incidence rates.

Key findings:

  • The incidence of IBD decreased from 1990 when it was 23.6 per 100,000 to 16.2 per 100,000 in 2012.
  • In the study period (1990-2012), there were 3114 cases of CD and 3499 cases of UC diagnosed in Manitoba

In the discussion, the authors speculate on the reasons for the decline in IBD incidence in an area with high rates of IBD.  Some of the change may be related to changes in the population mix –more immigrants from areas with lower rates of IBD.  In the editorial, it is noted that a recent systematic review (Lancet 2018; 390: 2769-78) indicated that the “incidence of IBD is stabilizing in Western countries.”

My take: There are a lot kids and adults with IBD.  The preponderance of epidemiology studies point to increasing incidence and prevalence.

Related blog posts:

Rock art during “social distancing”

Silent Anal Fistulas –Sounds Bad, Is It?

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A recent prospective study (PH Kim et al. Clin Gastroenterol Hepatol 2020; 18: 415-23) with 440 consecutive adults (mean age 29.6 years) with Crohn’s disease (CD) identified asymptomatic anal fistulas with MRE (including anal MRI) studies. 36 patients were newly diagnosed and the remainder had established CD.

Key findings:

  • In all of these patients, none of whom had clinical fistulas, an MRE identified “perianal tracts” in 53 (12%).
  • 37 of 290 (12.8%) of patients without a perianal fistula history and 16 of 150 (10.7%) with a history of healed perianal fistula had perianal tracts identified on MRE
  • No patients had any lesions that required treatment after examination by a surgeon
  • MRE detection of asymptomatic tracts was independently associated with later need for perianal treatment: 17.8% cumulative incidence at 37 months (aHR 3.06)

My take: Abnormal perianal tracts on MRE in asymptomatic patients indicate an increased risk of developing clinically-significant perianal disease –though most do not.

More on COVID19:

  • No children with IBD have been reported thus far from ESPGHAN which includes a 100 sites (mainly Europe) (as of March 10th); to report cases: ESPGHAN COVID19 Case Report Page
  • There is some discussion that biologic therapy for IBD may have some protective effects

 

 

Working Together to Improve Outcomes for Children with Inflammatory Bowel Disease

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Recently, we had an “ImproveCareNow Population Management” meeting.  At these regular meetings, we typically review at least one topic of interest, review data on how patients are doing (eg. hospitalizations, clinical remission, surgeries, followup visits), and discuss patients who have challenging clinical problems.  Credit for making these meetings work go to Clair Talmadge, PA-C, Samantha Gomez (ICN coordinator), and Chelly Dykes (physician leader).  Also, with regards to depression screening, we are fortunate to have the support of Bonney Reed-Knight and Jessica Buzenski.

At the latest meeting, we discussed our recent implementation of depression screening, expanded definitions of clinical remission/sustained clinical remission, and family support projects.

With regard to depression screening, we are finding that ~30% had actionable screens indicating some level of depression and ~4% screened as suicidal (requiring urgent attention).

My take: Each of these meetings and the work that goes into them make tangible improvements in outcomes.

Some of the slides are shown below.

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.

IBD and Immune-Mediated Diseases

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J Burisch et al. Clin Gastroenterol Hepatol 2019; 17: 2704-12.  In this nationwide cohort from Denmark with 14,377 adult patients with IBD (median age 45.8 yrs) and 71,885 controls; immune-mediated diseases (IMID) were present in 22.5% of those with IBD.

Most common IMID:

  • psoriasis
  • asthma
  • type 1 diabetes
  • iridocyclitis

Other IMID:

  • multiple sclerosis
  • pyoderma gangrenosum
  • rheumatoid arthritis
  • ankylosing spondylitis,
  • celiac
  • primary scelorsing cholangitis,
  • primary biliary cholangitis
  • sarcoidosis
  • Graves’ disease

Findings:

  • Patients receiving infliximab were at a reduced risk of developing an IMID with aOR of 0.52 for Crohn’s disease (CD) and 0.47 for Ulcerative Colitis. (UC)
  • 80.3% of IMID were noted prior to onset of IBD
  • The presence of IMID was associated with an increased risk of surgery in patients with CD with aOR of 2.30 but not in patients with UC

My take: About 1 in 4 patients with IBD have at least 1 other immune-mediated disease.  The presence of an immune-mediated disease is associated with a higher likelihood of needing a biologic therapy and with surgery in patients with Crohn’s disease. In patients with numerous immune-mediated diseases, one needs to consider the possibility of other etiologies (eg. CTLA4 defiency)

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Saint Jerome (not far from Montreal)

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

Fewer Surgeries with Crohn’s Disease

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Briefly noted: NE Burr et al. Clin Gastroenterol Hepatol 2019; 17: 2042-49.

In a retrospective cohort (1994-2013) using a primary care database from England, the authors identified decreasing risk of surgeries with Crohn’s diseae (CD).

  • From 1994-2003, the risk of first surgery dropped from 44% to 21%.
  • The risk of a second resection dropped as well, from 40% in 1994 to 17% in 2003 (with 10-year followup)

The reasons for this reduction are not certain but could include better clinical care or reduction in other risk factors (like smoking).

Atlanta Botanical Garden

Dietary Therapy for Inflammatory Bowel Disease –Useful Update

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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

 

Good Food and Bad Food for Crohn’s Disease -No Agreement

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As noted in a previous blog (IBD Briefs August 2019), there have been numerous diets proposed to help with Crohn’s disease.   The chart below illustrates the lack of any consensus.

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Canadian Pediatric Guidelines for Crohn’s Disease

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DR Mack et al. Gastroenterol 2019; 157: 320-48. Full Text: Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn’s Disease

“When the consensus group met in October 2017, the most recent consensus guidelines for the treatment of CD in pediatric patients were those from” ESPGHAN/ECCO in 2014 with data from June 2013. Thus, the guideline attempts to provide more updated information and recommendations based on incorporating the latest studies.

The authors provide 25 consensus statements.  Here are a few of interest:

  • Recommendation 9: In patients with CD, we suggest exclusive enteral nutrition to induce clinical remission (Recommendation 6 recommends steroids as a treatment for clinical remission; adult Canadian guidelines recommended against using exclusive enteral nutrition)
  • Recommendation 11: In patients with CD in remission, we suggest that if partial enteral nutrition is used it should be combined with other medications to maintain clinical remission.
  • Recommendation 20: When starting infliximab in males, we suggest against using it in combination with a thiopurine.
  • Recommendation 24: In patients with moderate to severe CD who fail to achieve or maintain clinical remission with anti-TNF–based therapy, we suggest ustekinumab to induce and maintain clinical remission.
  • Recommendation 25: In patients with CD, we recommend against cannabis or derivatives to induce or maintain remission.

In addition, the authors provide 13 statements with no recommendations -here are two of them:

  • No consensus J: When starting infliximab in females, the consensus group does not make a recommendation (for or against) regarding combining it with a thiopurine to maintain a durable clinical remission.
  • No consensus L: In patients with CD who have achieved a clinical remission with anti-TNF therapy, the consensus group does not make a recommendation (for or against) regarding assessment for mucosal healing within the first year to determine the need to modify therapy.

Crater Lake, OR

IBD Briefs August 2019

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A Levine et al. Gastroenterol 2019; 157: 440-50.  This study found that a Crohn’s Disease Exclusion Diet plus partial enteral nutrition induced sustained remission in a 12-week prospective randomized controlled trial with 74 children.  At week 12, “76% of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given” EEN followed by PEN.  The associated editorial on pages 295-6 provides a useful diagram of various dietary therapy components for a large number of diets that have been given for IBD.  The editorial recommends:

“For now, simple dietetic recommendations such as consuming a well-balanced diet prepared largely from fresh ingredients and thereby avoidance of emulsifiers and additives and processed foods are appropriate for all patients.  In select patients,…a trial of dietary therapy alone with a diet such as CDED could be attempted for a short period of time, with close follow-up, and with agreement with the patient that failure to fully respond is an indication to escalate therapy.”  More dietary trials are ongoing.

Related blog posts:

NJ Samadder et al Clin Gastroenterol Hepatol 2019; 17: 1807-13. In this cohort from Utah 1996-2011 with 9505 individuals with IBD, 101 developed colorectal cancer.  Standardized incidence ratio (SIR) for CRC in patients with Crohn’s disease was 3.4, in ulcerative colitis 5.2, in patients with primary sclerosing cholangitis 14.8.  A family history of CRC increased the risk of CRC in patients with IBD to 7.9 compared to general population.  Family hx/o CRC increased the SIR by about double the CRC risk in IBD patients without a family hx/o CRC.

CR Ballengee et al. Clin Gastroenterol Hepatol 2019; 17: 1799-1806. In this study with 161 subjects from the RISK cohort, the authors found that elevated CLO3A1 levels in subjects with CD was associated with the development of stricturing disease but was not elevated in those with strictures at presentation and in those who did not develop  strictures.

AL Lightner et al IBD 2019; 25: 1152-68.  Short- and Long-term Outcomes After Ileal Pouch Anal Anastomosis in Pediatric Patients: A Systematic Review.  This review included 42 papers.

  • Rates of superficial surgical site infection, pelvic sepsis, and small bowel obstruction at <30 days were 10%, 11%, and 14% respectively.
  • Rates of pouchitis, stricture, chronic fistula, incontinence and pouch failure were 30%, 17%, 12%, 20% and 8% respectively with followup between 37-109 months.
  • Mean 24-hour stool frequency was 5.

MC Choy et al IBD 2019; 25: 1169-86.  Systematic review and meta-analysis: Optimal salvage therapy in acute severe ulcerative colitis.  Among 41 cohorts (n=2158 cases) with infliximab salvage, overall colectomy-free survival was 69.8% at 12 months.  The authors could not identify an advantage of dose-intensification in outcomes, though this was used more often in patients with increased disease severity, “which may have confounded the results.”

Hood River, OR

Combination Therapy Study Points to Central Role of Adequate Drug Levels

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A recent study (JF Colombel et al. Clin Gastroenterol Hepatol 2019; 17: 1525-32) examines the effect of combination therapy and drug levels in achieving corticosteroid-free remission at week 26 (CSFR26).

The authors performed a post hoc analysis from 206 patients with Crohn’s disease (CD): 97 monotherapy with infliximab & 109 with combination infliximab/azathioprine

Key findings:

  • The proportions of patients achieving CSFR26 were not significantly greater among those receiving combination therapy vs monotherapy within the same serum infliximab concentrations
  • Mean trough infliximab concentrations in the combination therapy were higher than for monotherapy: 3.54 mcg/mL vs. 1.55 mcg/mL
  • Higher levels of antidrug antibodies were seen with monotherapy: 35.9% vs 8.3% of those with combination therapy.  Antidrug antibodies were detected only in those with lowest quartile of infliximab trough levels.

My take: This study indicates that combination therapy’s higher efficacy is due to  favorable pharmacokinetics rather than drug synergy.  If good infliximab trough levels can be achieved with infliximab monotherapy, this may obviate the need for combination therapy.  The uncertain factor is whether closer attention to trough levels will minimize the development of antidrug antibodies as effectively as the use of combination therapy.

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.

Sagrada Familia, Barcelona