Gastroenterology
Ulcerative Colitis
Biomarkers in Ulcerative Colitis
The gold standard for diagnosing and monitoring ulcerative colitis has long been endoscopy, but work is being done to identify and develop less invasive biomarkers. Fecal calprotectin and intestinal ultrasound are currently the most promising noninvasive strategies emerging in clinical practice.
Biomarkers have become important in understanding whether a patient with ulcerative colitis has reached a true biologic remission in addition to a clinical symptom remission, which we know improves outcomes. Endoscopy is the gold standard, but it is an invasive test, so it may not be desirable for frequent use or appropriate for all patients, such as women who are pregnant. The biomarker of choice for ulcerative colitis in my practice is fecal calprotectin. Serum-based biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate are not necessarily reliable, as these can vary with other systemic illnesses. Someone can have significant inflammation without an elevated CRP, and CRP is also not specific to inflammatory bowel disease.
Fecal calprotectin has better sensitivity and specificity for colonic inflammation and can be used both at the time of diagnosis and for serial monitoring in established ulcerative colitis. An elevated fecal calprotectin in a patient with gastrointestinal symptoms such as diarrhea or bleeding should prompt gold-standard evaluations for ulcerative colitis, including a colonoscopy. Fecal calprotectin can also be helpful in patient monitoring. If someone has an elevated fecal calprotectin at baseline and you start them on a therapy, you can follow that biomarker over time to ensure that their condition improves. This can help you modify dosing or potentially even change the class of therapy. In addition, if someone with established ulcerative colitis has symptoms such as increased cramping or frequency without blood in their stool, and they have a fecal calprotectin of less than 50 μg/g, that can help one decide on an approach to management that may target noninflammatory symptoms.
One of the problems with fecal calprotectin is that it is difficult to obtain. Patients have to collect a stool sample and bring it to an outpatient laboratory. Even though these are now more common throughout the United States, the collection is messy and not something that patients necessarily want to do. I think that many patients are much more understanding once you explain its importance, but there may be easier ways to do this in the future, such as at-home testing. There can be some variability in threshold levels for fecal calprotectin, so it is most useful when used serially so that you can see deviations from a patient’s particular range. A monitoring paradigm using both biomarkers and clinical symptoms to inform treatment may be an improvement over using symptoms alone.
The other noninvasive test that I find reliable and use in my practice is intestinal ultrasound, which looks at bowel wall thickness and vascularity (via Doppler signal) associated with inflammation. Intestinal ultrasound can be used serially to assess response to therapy. Normal bowel wall thickness and an improvement in hyperemia have been shown to correlate with endoscopic remission.
Even 5 years ago, fecal calprotectin was not as utilized as it is now, and testing of calprotectin is recommended in American Gastroenterological Association guidelines and is now better covered by insurance. While we do not have effective biomarkers to predict response to specific therapies, noninvasive strategies including biomarkers can be effectively used to monitor response to therapy. Right now, the combination of fecal calprotectin and intestinal ultrasound is where the field is headed.
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