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

 

Efficacy of Anti-TNF Agents for Internal Fistulas and Study of Antibiotics and Development of IBD

G Bougen et al. Clin Gastroenterol Hepatol 2020; 18: 628-36.  This retrospective study (n=156, median age 32 years) found that anti-TNF therapy delays or prevents surgery for almost half of patients with Crohn’s disease who had luminal fistulas.  Key findings:

  • With a median followup of 3.5 years, “68 patients (43.6%) underwent a major abdominal surgery.”
  • Fistula healing occurred on average 1 year after the introduction of anti-TNF treatment
  • The presence of a stricture or abscess increased the likelihood of surgery.
  • Three patients died from intestinal adenocarcinomas, one patient died from melanoma (6 months after initiation of anti-TNF therapy), one patient died from sepsis (3 months after initiation of anti-TNF therapy, and 32 patients (20.5%) developed an intestinal abscess.

My take: Therapy with anti-TNF agent, in the setting of a luminal fistula, is a reasonable option, especially in the absence of a concurrent stricture.

FS Troelsen, S Jick. Inflamm Bowel Dis 2020; 26: 440-7, editorial 448-9. Using a UK database, the authors identified 461 cases of ulcerative colitis (UC) and 863 cases of Crohn’s disease (CD) and then matched each case to 4 controls. Key findings:

  • There was no association between ever use of antibiotics and UC, OR 1.02 or CD, OR 1.01 compared to never use of antibiotics
  • CD was associated with antibiotic exposure before age 5 (OR 2.2) in analysis restricted to individuals followed from birth
  • A slight increase was seen for CD in ever users of quinolones (OR 1.76, CI 1.00-3.11) and metronidazole (OR 1.43, CI 0.87-2.34)

In the editorial, Charles Bernstein notes that “it may be that specific types of antibiotics…at specific times in a person’s life have differential risks for IBD development. Also, it may be that what triggers IBD in children is different than what triggers IBD later in life.”

Duke University -late Fall 2019

Ups (mostly) and Downs with IBD Epidemiology

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.

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Rock art during “social distancing”

Silent Anal Fistulas –Sounds Bad, Is It?

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

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

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

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