Capsule Endoscopy More Sensitive than MRE for Crohn’s Disease

Briefly noted: B Gonzalez-Suarez et al. IBD 24: 775-80.

In 47 patients with established (n=32) or suspected Crohn’s disease (n=15), MRE was first performed to exclude strictures and then subsequently capsule endoscopy (CE) (with patency capsule in 10 patients). Key finding: Small bowel lesions were found in 36 of 47 with CE compared with 21 of 47 with MRE (76.6% vs 44.7%, P=0.001)

Related blog post: Head-to-Head: Capsule endoscopy compared to colonoscopy

Here’s What I Really Want to Know about an MRE Study –What is the Correlation with PGA?

A nice pediatric study (CG Sauer et al. JPGN 2016; 62: 378-83) provides data on 101 children from a single center who underwent MRE to evaluate their Crohn’s disease.  This study was a retrospective chart review using a prospectively maintained MRE database.  All of the children in this study underwent MRE greater than 180 days after diagnosis.  MRE was ordered at the discretion of the treating gastroenterologist. Median followup was 2.8 years after MRE.

Key findings:

  • MRE correlated with meaningful clinical outcomes. Of the 65 with active inflammation on MRE, only 44.6% achieved clinical remission (another 30% progressed to mild disease activity). Of the 36 without active inflammation, 88.9% achieved clinical remission.
  • Children with active inflammation on MRE were more likely to undergo surgery (18.5% vs. 2.8%) and more likely to have medication changes (44.6% vs. 8.3%).

While this population may have had more disease than those who did not undergo MRE (since it was done at the discretion of gastroenterologist), what would interest me would be the correlation with the physician global assessment.  A rough calculation would suggest that only 40% of these patients achieved a clinical remission which is well below ImproveCareNow reported benchmarks, but not much different from previous studies using objective markers.  Furthermore, it would be of interest to look at whether individual clinicians incorporated their abnormal MREs into their assessment of PGA.  If the patient was doing well clinically but their MRE was markedly abnormal or even mildly abnormal, were these patients classified as in remission or otherwise.

My take: MRE is an excellent & expensive tool to assess for mucosal healing.  As our treatments continue to improve, MRE will be useful to monitor our progress.  How we incorporate our objective markers with our clinical markers needs further work.

Related blog posts:

 

Moving to MRE

A recent review (JPGN 2014; 59: 429-39) regarding imaging for inflammatory bowel disease reiterates the accepted view that magnetic resonance enterography (MRE) is typically the most useful imaging test for children with inflammatory bowel disease; in Table 5, MRE is listed for each indication, though CT scan is recommended “if emergent or after hours.”  The review reviews prior pediatric publications, radiation risks (with non-MRE studies), and alternative imaging.  The discussion on costs is minimized, though the authors note that MRE is the most expensive and can be compromised by motion artifact. As a practical matter, I think giving a typical charge (or range) for each of the imaging techniques would be helpful.  Also, another important issue is assuring that radiologists have the technical expertise to obtain quality imaging.

Another study (Clin Gastroenterol Hepatol 2014; 12: 1702-07) retrospectively looked at 1095 emergency room visits by 613 individuals (average age ~40 years) to determine if they could develop a model to limit unnecessary CT scans.  Of the 1095 CT scans, 24.8% were normal; 10.9% had either perforation or non-perianal abscess.  In their discussion, they note that the equation “no scan for ESR (mm/h) + 5*CRP (mg/dL) ≤10” would avoid 18.5% of CT scans.  Implementation of a more complex model could eliminate up to 43% of the CT scans.  The algorithm (Figure 2) suggested by the authors:

  • Assess for obstruction.  If suggestive symptoms, obtain abdominal X-rays.  If concerns for obstruction remain, consider CT scan.
  • If not concerned about obstruction, is there a high likelihood of perforation or abscess? If yes proceed with CT scan.  If not, consider anti-inflammatory therapy if CD symptoms present (without imaging).

Here’s the link to the abstract –supplementary materials can be obtained by those who log in.   http://dx.doi.org/10.1016/j.cgh.2014.02.036

Bottomline: Cross-sectional imaging is particularly helpful at determining whether complications are developing in patients with inflammatory bowel disease.  Increasing use of MRE will reduce radiation risks.

With regard to costs, a recent NPR story discussed “How Much Is That MRI, Really? Massachusetts Shines A Light.” While this story discussed costs related to a Massachusetts law which mandates that insurers reveal the costs of various tests, it did not relate any information regarding quality.  The study implied that an MRI at one institution would be equivalent to an MRI at another.  This is not the case.

Related blog posts:

NASPGHAN Notes –Last Word for this Year

This blog entry has abbreviated/summarized several presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

IBD Treatment: Targets for the Modern Age –Eric Benchimol (Children’s Hospital of Eastern Ontario)

Goal: Review mucosal healing and best targets to measure to predict prognosis

Treat-to-target:

  • Regular assessment of disease activity using objective outcome measures.
  • Adjust treatment if not accomplishing goal.
  • Proven helpful in rheumatoid arthritis, hypertension, diabetes, and hypercholesterolemia.

Old targets:

  • “Clinical remission”
  • “Feeling better”
  • Indices: PCDAI, CDAI, Harvey-Bradshaw
  • Problem: Active disease is not well-predicted by symptoms or laboratory markers
  • 2nd Problem: Active symptoms not always due to active IBD (could be due to functional complaints)
  • PUCAI score in ulcerative colitis does reflect ulcerative colitis severity fairly well

New Targets

  • High correlation with outcomes
  • Cost-effective
  • Available

Is mucosal healing achievable?   If you were scoped and adjustments made in therapy, then much higher rate (HR >4) of remission. Bougen, Clin Gastroenterol Hepatol 12: 978.  Endoscopy may be best way to assess mucosal healing.  Since it is invasive, efforts have been made to identify surrogate markers.

Treat-to-Target Algorithm

Treat-to-Target Algorithm

Surrogate Markers

  • Ultrasound –can be useful but operator-dependent
  • MRE had 83% accuracy for endoscopic remission: Gastroenterol 2014; 146: 374.
  • Calprotectin not as accurate in children? Am J Gastroenterol 2014; 109: 637. Sensitivity high 97%, specificity for remission 68%
  • CRP –if elevated, higher risk of complications or surgery. However, sensitivity is much lower for disease activity than calprotectin/imaging studies for active disease
  • Drug levels. Therapeutic IFX trough levels (and adalimumab) are highly predictive of mucosal healing.

Bottomline (my interpretation): Resolution of clinical symptoms and improvement in bloodwork is not good enough.  When/timing to assess with sensitive surrogate markers is still uncertain.  In many patients, endoscopy is needed to assure adequate improvement; however, in others, a followup imaging study (eg. MRE) or sensitive stool assays may be the best approach.

A related story (from AGA’s Today in Medicine email feed & pointed out to me by Ben Gold) indicates that estimation of clinical symptoms is not accurate:

Survey Suggests Severity Of IBD Is Underestimated By Gastroenterologists.

MedPage Today (10/31, Walsh, 186K) reports that survey results presented at a medical conference indicate that “the severity of inflammatory bowel disease is significantly underestimated by gastroenterologists.” Researchers found that “a total of 55% and 67% of physicians who participated in a web-based survey rated cases of Crohn’s disease and ulcerative colitis as being mild when they were actually moderate.” Meanwhile, “for case studies that represented severe disease, 76% and 81% of the physicians gave ratings of either moderate or mild for Crohn’s disease and ulcerative colitis, respectively.”

 

Related blog posts:

Risk Stratification in Pediatric IBD: Are we there yet? Jeffrey Hyams (Connecticut Children’s

Initially, Dr. Hyams described the exploding head syndrome; many attendees might have thought they had this due to information/”big data” overload, but this syndrome is a sleep disorder/parasomnia event.  Here’s a link to the image from his talk.  Then, Dr. Hyams reviewed data on risk stratification:

  • Mutations: Some genetic mutations are associated with disease severity
  • Still needed: specific pediatric data
  • Microbiome: Some profiles associated as prognostic factors in pediatric RISK study
  • Early anti-TNF associated with improved outcomes (using propensity analysis) Gastroenterol 2014; 146: 383.

Bottomline: Not there yet with risk stratification. Many factors environmental, genetic susceptibility, immune response, and treatment need to be sorted out with “big data.”

Key Clinical Questions for your practice at this time:

  • Does this patient have known risk factors for doing poorly?
  • Am I using current therapies properly?
  • What is the risk of undertreated disease? This needs to be considered with discussion of safety of IBD meds.

Cross Examination of Cross-Sectional Imaging in IBD –Sudha Anupindi (Radiology/CHOP)

  • For the most part, barium studies discouraged (eg. UGI/SBFT) by speaker; radiation ~1 mSv.
  • CT (conventional) widely available and easy –if needed urgently/middle of night.

Initial presentation: imaging of choice

  • MR enterography –no radiation, better contrast resolution, best for perianal disease, able to evaluated peristalsis. Two limitations: cost, interpretation
  • CT enterography –fewer motion artifacts (0.6 seconds), lower cost, increased availability, better spatial resolution radiation reduced with current technology at most Children’s hospitals: 1-2 mSv

Abdominal ultrasound holds promise as alternative imaging with lower cost.

 

ESPGHAN IBD Diagnostic Practice Recommendations -Revised Porto Criteria

Recently ESPGHAN assembled an international group of European experts in pediatric inflammatory bowel disease (PIBD) to establish practice recommendations (JPGN 2014; 58: 795-806).  Their aim was “to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD.”

Before detailing some of their recommendations, I want to state my main criticism: these recommendations do not consider cost or cost-effectiveness. This is important since we do not live in a world where costs are irrelevant.

Some specific recommendations/observations:

1. “We recommend performing small bowel imaging in all suspected cases of IBD at diagnosis; this may be deferred in typical UC.”  In addition, all suspected cases of IBD should undergo esophagogastroduodenoscopy (EGD) and ileocolonoscopy.  “The diagnostic yield of an EGD to diagnose Crohn’s disease (CD) in patients with an otherwise normal workup [ileocolonoscopy/small bowel imaging] is ~7.5%. ”

2. The authors clarify the use of IBD-unclassified (IBD-U). “IBD-U should be …for patients with colitis and highly atypical findings.” Atypical findings for ulcerative colitis: include rectal sparing, and cecal patch (present in 2% of pediatric patients with left-sided colitis).  Table 3 suggests that if at least one “class 2” (rare feature) exists or at least 2 “class 3” (uncommon) feature exists, then labeling IBD-U is appropriate.

Rare (Class 2):

  • significant growth delay
  • histologic and gross sparing of rectum
  • transmural inflammation in the absence of severe colitis
  • duodenal or esophageal ulcers (not due to other causes)
  • multiple aphthous ulcerations in the stomach (not due to other causes)
  • positive ASCA in the presence of negative pANCA
  • mucosal inflammation more severe in proximal colon

Uncommon (Class 3):

  • severe scalloping of stomach or duodenum (not due to other causes)
  • focal chronic duodenitis (not due to other causes)
  • aphthous ulcerations in the colon

3. Crohn’s disease, according to Table 3, should be diagnosed with any of the following:

  • well-formed granulomas anywhere in the GI tract, remote from a ruptured crypt
  • deep serpentine ulcerations, cobblestoning or stenosis anywhere in the small bowel
  • fistulizing disease
  • ileal inflammation in the presence of normal cecum

4. “Normal blood tests do not exclude the diagnosis of IBD”… Fecal markers (eg. calprotectin) are “extremely sensitive in the detection of mucosal inflammation but are not specific for IBD.”

5.”Although small bowel imaging is encouraged in all of the patients with suspected IBD, it is essential in pediatric patients with CD, IBD-U, or atypical UC.”  Magnetic resonance enterography (MRE) is currently the imaging modality of choice in PIBD.  Wireless capsule endoscopy (WCE) is a “useful alternative.”  The authors advocate for imaging because it may “detect small intestinal involvement…and identify disease complications.”

6. Evaluation for primary immune deficiency should be performed in all cases of PIBD  diagnosed <2 years of age.

While the authors acknowledge that “clinical considerations may require taking a course of action that varies from these criteria,” nevertheless, they are likely to influence clinical practice.  My personal belief is that there are many situations in which small bowel imaging will not result in changes in clinical care.  Furthermore, many patients, especially younger patients, would require anesthesia in order to complete a MRE which is an added burden.  In addition, with the added emphasis on assessing response to therapy, one could envision that some patients would be better served with imaging after implementing treatment.

Related blog posts:

 

 

 

Superiority of Anti-TNF Therapy in Children

This study’s conclusion comes as no surprise:

“In children newly diagnosed with comparably severe CD, early monotherapy with anti-TNFα produced better overall clinical and growth outcomes at 1 year than early monotherapy with an immunomodulator. Further data will be required to best identify children most likely to benefit from early treatment with anti-TNFα therapy.”

Here’s the reference:

Gastroenterology Volume 146, Issue 2 , Pages 383-391, February 2014

Here’s a link to the full text article:  Increased Effectiveness of Early Therapy with Anti-Tumor Necrosis Factor-α Versus an Immunomodulator in Children with Crohn’s Disease

Methods: “From 2008 through 2012 at 28 pediatric gastroenterology centers in North America. Patients were managed by physician dictate. From 552 children (median age, 11.8 y; 61% male; 63% with pediatric CD activity index scores >30; and median C-reactive protein level 5.6-fold the upper limit of normal), we used propensity score methodology to identify 68 triads of patients matched for baseline characteristics who were treated with early anti-TNFα therapy, early immunomodulator, or no early immunotherapy.”

Another reference/link from same issue:

Accuracy of Magnetic Resonance Enterography in Assessing Response to Therapy and Mucosal Healing in Patients with Crohn’s Disease