Gil Melmed, MD, on Noninvasive Monitoring in IBD

Dr Melmed reviews the noninvasive options available to clinicians to monitor disease activity in inflammatory bowel disease, including biomarkers, stool testing, and imaging modalities.

Gil Y. Melmed, MD, is director of Inflammatory Bowel Disease Clinical Research and codirector of the Clinical Inflammatory Bowel Disease program at Cedars-Sinai Medical Center in Los Angeles, California.

Hi, I'm Dr. Gil Melmed. I'm speaking to you from Advances in IBD from Orlando, Florida, and I'm from Cedars-Sinai in Los Angeles. I had the opportunity to present on noninvasive monitoring strategies for inflammatory bowel disease with several colleagues. And what we did was go through ways that we can determine disease activity on an ongoing basis, longitudinally in patients with both Crohn's disease and ulcerative colitis, in order to determine optimal strategies for when and with what to monitor rather than doing invasive colonoscopy.

Clearly, colonoscopy is a gold standard and something that in treat to target paradigms and algorithms is used to determine disease activity and also to determine whether or not targets of mucosal healing have been achieved. But of course, we as clinicians and certainly our patients would prefer to monitor patients noninvasively.

First, we discussed CRP, C-reactive protein, which was presented by Dr. Parambir Dulai from Northwestern in Chicago. And we discussed that C -reactive protein as a blood test has excellent discriminatory predictive capabilities with respect to its ability to identify inflammation versus no inflammation, both as a qualitative marker, positive or negative, and as a quantitative marker in terms of how high the CRP can go, gives us a sense of perhaps the severity of inflammation and this can be seen certainly in Crohn's disease but also in ulcerative colitis. And one of the strongest advantages of CRP as a monitoring tool, argued Dr. Dulai, was that CRP as a blood test is something that is very likely to be done. Of course we want to use a test that's going to be done and as a blood test it's relatively easy and relatively noninvasive, doesn't have the yuck factor, if you will, that a stool test might have, doesn't require any special expertise, and so is very likely to be done if it's ordered by the clinician.

We next talked about stool biomarker-based testing, i.e. fecal calprotectin, that was presented by Dr. Harold Boutte, also from Northwestern in Chicago. And looking at calprotectin as a very sensitive marker for determining inflammation for inflammatory bowel disease. We talked about both colonic disease, UC and colonic Crohn's, as perhaps having the most sensitive utility for fecal calprotectin, but also that calprotectin can be effective in monitoring for patients with ileal Crohn's disease, albeit perhaps with lower overall levels. He talked about a gray zone of 100 to 300 as a result that sometimes might be a little bit more difficult to interpret, but with levels below that as being remarkably suggestive of healing and levels above 300, remarkably suggestive of active inflammation, again with quantitative numbers that can go up as the severity of inflammation progresses.

We talked about STRIDE 2 recommendations that utilize a combination of both CRP and stool calprotectin as well as some clinical trials, for example, like the CALM study and the REACT 2 trial that demonstrated the utility of biomarker-based testing as ways of monitoring patients over time, and again, both for Crohn's disease and ulcerative colitis.

One practical tip we learned about for fecal calprotectin was that the optimal time or the optimal way to assess fecal calprotectin is by having patients take the sample first thing in the morning with the first stool of the day—whenever that might be, actually—in order to maintain some kind of reproducibility as well as trying to get the testing done at the same lab over time so that the patient has consistent lab results without succumbing to some of the variabilities across testing platforms that can be seen in different commercial labs.

We next talked about other imaging modalities, specifically small bowel and intestinal ultrasound and cross-sectional imaging. Dr. Maia Kayal from Mount Sinai in New York talked about intestinal ultrasound as an emerging modality with some degree of training that is required in order to have facility and expertise enough for the practitioner at point of care, the gastroenterologist at the point of care, to be able to determine disease activity with remarkable correlation with what might be seen on colonoscopy or even cross-sectional imaging, both in the colon for ulcerative colitis, as well as in the ileum, certainly the terminal ileum for Crohn's disease. Looking at 2 specific parameters, bowel wall thickness and hyperemia as seen on Doppler, the utility of intestinal ultrasound can be very significant in being able to noninvasively tell us what is actually happening with respect to inflammation that could be seen on a colonoscopy. Advantages of ultrasound, certainly, that it's noninvasive, can be done at point of care, the patient can actually see what's happening, they don't need to wait for a result—are all advantages. But we also talked about that fact that access currently in the current state in the United States is relatively limited to centers that have ultrasound capabilities and expertise. But that this is a rapidly changing field with more and more centers and practices coming online with appropriate training and expertise and equipment for utility of intestinal ultrasound.

Dr. Ryan Stidham also argued for the utility of cross-sectional imaging with CT and MR enterography, perhaps can't be done as often as ultrasound might be done, both from a practicality standpoint, a cost standpoint, but also that things might take longer to demonstrate change, whereas an ultrasound could perhaps see change in a very short period of time, perhaps a couple of days in ulcerative colitis and a couple of weeks in Crohn's disease, we probably need to wait longer before reassessing with a CT or MR enterography to look for improvement in structural damage for inflammatory bowel disease on the order of 4 to 6 months, and perhaps even longer than that.

And then finally, Dr. Stidham also argued for good old clinical diagnosis and clinical acumen. Ask the patient how they're doing. Get a sense of what are their symptoms and for ulcerative colitis, unlike for Crohn's disease, the clinical presentation can tell us a lot about what may be happening on the inside and perhaps can be used certainly adjunctively with some of the other testing that we talked about as a noninvasive marker of what's actually happening in the patient with high discriminant capabilities for determining the utility of clinical judgment and symptoms relative to what might be seen on a colonoscopy. Resolution of diarrhea, resolution of stool frequency, resolution of bleeding, are all associated with improvement that can be seen on colonoscopy.

This however is different than in Crohn's disease where there is no correlation that is demonstrable between symptoms and colonoscopy, something that we as clinicians need to keep in mind that a patient's symptoms with Crohn's disease do not actually tell us what might be happening on the inside. So ultimately we came to the resolution that we need all of these modalities, practical terms with Crohn's disease or with ulcerative colitis when initiating treatment strategy, getting baseline parameters, a CRP, a calprotectin, if you have access to an ultrasound, understanding what thatclooks like, cross-sectional imaging if appropriate for Crohn's disease in order tocdetermine something that can be followed over time, not just waiting for that colonoscopy that might not be for another year, but using these noninvasivecmodalities in order to determine along the way, whether a patient is actually getting better. And if not, then to make adjustments accordingly or follow-up testing, perhaps advancing a colonoscopy sooner than it might otherwise be done if there is suspicion of recurrent inflammation that needs to be addressed therapeutically.