IBD Reviews: Role of Antibiotics and Data on Biomarkers

A clinical review, “Antibiotics in IBD: Still a Role in the Biological Era?” (O Ledder, D Turner, Inflamm Bowel Dis 2018; 24: 1676-88).  While this article provides a detailed review of the use of antibiotics for Crohn’s (including perianal disease), Ulcerative colitis and the effects on the microbiome, the potential use for very early onset (VEO) IBD caught my attention:

“We have recently begun considering oral vancomycin and gentamicin as sole firstline therapy in the rare form of infantile (ie <2 years of age) mild to moderate IBD, with promising success…this is merely investigational” at this time.  (Ref: Lev-Tzion R et al. Digestion 2017; 95: 310-13).

My take: Antibiotics can be a helpful adjunct therapy in both Crohn’s disease and Ulcerative colitis. It is unclear what role antibiotics will have for VEO-IBD.

A recent commentary (R Khanna et al, Inflamm Bowel Dis 2018; 24: 1619-23) examines the role of biomarkers.  While much of this topic has been reviewed extensively, I found the part about calprotectin helpful.  One of the topics with discrepant data has been the negative predictive value of calprotectin for detecting inflammatory bowel disease.  The data in this review:

  • From a meta-analysis in patients with symptomatic ulcerative colitis, calprotectin had a sensitivity of 0.88 and specificity of 0.79 compared to endoscopic inflammation.  For Crohn’s disease, the respective values were 0.87 and 0.67.
  • For histologic remission in ulcerative colitis, a study found that with a threshold of 155 mcg/g, calprotectin had a sensitivity of 78% and specificity of 71%.
  • Another study suggested that values <100 mcg/g indicate quiescent disease, values 100-250 suggest possible active inflammation, and values >250 mcg/g suggest active inflammation.
  • A cross-sectional study indicated that calprotectin ≥57  mcg/g had a sensitivity of 91% and specificity of 90% to identify endoscopically-active disease (Gastroenterol 2016; 150: 96-102)

My take: Sensitivity/specificity vary greatly based on the likelihood of disease; in populations at lower risk for IBD, a calprotectin has a high level of excluding active inflammation/IBD. In populations with IBD, levels more than 250 mcg/g indicate a high likelihood of active inflammation whereas levels between 100-250 are indeterminate.

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Delayed Pouch Closure in the Surgical Management of Ulcerative Colitis

B Kochar et al. Inflamm Bowel Dis 2018; 24: 1833-9.  This study reviewed prospectively collected data from 2011-2015 involving 2390 Ileal Pouch Anal Anastomosis (IPAA) surgeries for ulcerative colitis in those ≥18 years of age.  Two approaches were compared:

  1. ‘Traditional’ 2- stage IPAA where the pouch is created with the colectomy
  2. Or a 3-stage surgery where the pouch is created in a second surgery after the colectomy (delayed pouch creation)

Key findings:

  • Delayed pouch creation were significantly less likely to have an unplanned reoperation (RR =0.42, CI 0.24-0.75) and less likely to have major adverse events (RR=0.72, CI 0.52-0.99)
  • Those in the delayed pouch creation group were much less likely to be receiving chronic immunosuppression at the time of surgery –15% compared to 51% in 2-stage group

My take: Particularly for sicker patients, delayed pouch creation (3-stage procedure) is likely to be best approach.

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Catheter-Related Venous Thrombosis in Pediatric Patients with Inflammatory Bowel Disease

A recent retrospective study (CE Diamond et al. J Pediatr 2018; 198: 53-9) examined the issue of catheter-related venous thrombosis in pediatric inflammatory bowel disease (IBD) patients (2015-17).

In total, 40 patients (47 hospitalizations, median age 14 yrs) with IBD were reviewed.  At the discretion of the treating physician, anticoagulation therapy (AT) with enoxaparin was administered in some children due to the recognized increase risk of venous thromboembolism (VTE).  This protocol did NOT evaluate for subclinical venous thrombotic events.  Detection of VTE was undertaken in those who became symptomatic (eg. pain or swelling).

AT protocol: 

  • In patients less than 40 kg, the starting dose of enoxaparin was 0.5 mg/kg/dose SC every 12 hrs with anti-factor Xa levels drawn 4-6 hours after the patient had received at least 2 doses with a target level of 0.1-0.3 U/mL. The first dose was administered on the same day as CVC placement but after placement.
  • In patients >40 kg, a fixed dose of 40 mg of enoxaparin SC every 24 hrs without laboratory monitoring

Key findings:

  • 5 of 23 (22%) hospitalizations without AT developed VTE; in contrast 0 of 24 with AT prophylaxis.  Mean duration of AT was 11 days.
  • All five who developed VTE had complete resolution after treatment with anticoagulation Rx. No cases of genetic thrombophilia were identified.
  • Bleeding issues were similar in the two groups –46% of those receiving AT Rx required at least one blood transfusion compared with 39% who did not receive AT Rx.

Overall, these groups (with and without AT Rx) had similar demographic features and had severe active IBD.  Most were receiving biologic therapy and the majority were receiving steroids.  The authors observed a trend towards more use of AT over the study period, “suggesting increased comfort levels of treating physician…even in the presence of rectal bleeding.”

My take: This relatively small study found that AT Rx reduced the rate of CVC-related venous thrombosis.  A larger prospective study is needed to confirm the potential benefit of AT treatment.

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Artwork near Azalea Drive/Chattahoochee river

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.

IBD Shorts August 2018

Vitamin D Receptor Signaling in IBD. Inflamm Bowel Dis 2018; 24: 1149-54.  This article reviews the ways vitamin D/vitamin D receptor may contribute to the genetic, environmental, immune, and microbial aspects of IBD.

LY Chi et al. Inflamm Bowel Dis 2018; 24: 1344-51. This study with 223 pediatric patients & young adults found that current or prior combination therapy with infliximab, compared to monotherapy resulted in higher infliximab levels and lower antibody formation. Combination agent was mainly methotrexate (n=71) rather than thiopurine (n=13). In those with infliximab dose <10 mg/kg, those currently receiving combination therapy had median level of 11.1 compared with 7.0 for prior combination and 5.86 for monotherapy (never combination).

CM Johnson et al. Clin Gastroenterol Hepatol 2018; 16: 900-7.  In this retrospective study with 1466 patients with Crohn’s disease, the subset of patients with granulomas (n=187, 12.8%) were associated with a more aggressive phenotype and a younger age at diagnosis (23.6 years compared with 27.9 years; P= .0005). These patients had higher rates of steroid use, narcotic use, more stricturing and penetrating disease along with increase rates of surgery.

 

MRE Does Not Fare Well at Detecting Lesions Evident on Upper Endoscopy

A recent study (PC Church et al. JPGN 2018; 67: 53-8) examined how well EGD findings were detected by MRE in 188 children (mean age 14 years).

Key findings:

  • EGD was macroscopically abnormal in 93 (49%) with ulcerations being the most common abnormality in 66 (35%).
  • In contrast, the local radiologist identified UGI inflammation in 7 (4%) and the central radiologists identied UGI inflammation in 20 (22%).  “There was no agreement between local and central radiologists when examining the UGI as a whole (κ=-0.02, P-0.59)”
  • The local radiologists “correctly identified only 5 of 93 (8%) patients with UGI findings on EGD.”  The central radiologists “correctly identified 9 of 45 (30%) patients with UGI findings on EGD.”

The authors state that “the Porto criteria mandate the performance of EGD for all pediatric patients suspected of having IBD. Our study has demonstrated that MRE cannot be relied upon as the sole method of evaluating the UGI.”

My take: For those who take care of children with IBD, this study will not come as a surprise as many of the UGI findings (found at endoscopy) are subtle.  This study does quantify the much higher sensitivity of endoscopic evaluation and is similar to studies that have compared capsule endoscopy to MRE.

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Cumberland Island 2018

Serology Titers Associated with Clinical Expression of Ulcerative Colitis in Children

Briefly noted: A recent study (EA Spencer et al.Inflamm Bowel Dis 2018; 24: 1335-42) examined phenotype and serology in 399 children with newly diagnosed ulcerative colitis (PROTECT study).

Key findings:

  • 65% had positive serology for pANCA; 62% in those <12 and 66% in those ≥12 years
  • 19% had positive serology for anti-CBir1; 32% in those <12 and 14% in those ≥12 years
  • High titer (≥ 100)) pANCA positivity was associated with more extensive disease but not with PUCAI values or Mayo endoscopic subscores.

My take: The serology titers for IBD, in my view, have academic interest but do not routinely enhance patient care.

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Amelia Island