Aug. 22, 2024
Ulcerative colitis (UC) is an idiopathic chronic or relapsing condition characterized by immune activation and mucosal inflammation in the colon and rectum. Left untreated, UC can decrease an individual's quality of life and elevate the risk of hospitalization, colectomy and colorectal cancer.
Typically, patients being treated for UC must undergo multiple colonoscopies to assess disease activity and monitor the response to treatment. Although colonoscopy is a safe procedure with a relatively low complication rate, the need for bowel preparation and the risks associated with sedation have prompted the search for a less invasive means of assessing UC activity.
"Over the years, we have recognized that making treatment changes based on symptoms alone might not be the ideal approach to therapy, because there isn't a one-to-one relationship between symptoms and the actual degree of inflammation in the bowel," explains Mayo Clinic gastroenterologist Edward V. Loftus Jr., M.D. Dr. Loftus is co-director of the Advanced Inflammatory Bowel Disease Fellowship at Mayo Clinic in Rochester, Minnesota, and the Maxine and Jack Zarrow Family Professor of Gastroenterology Specifically for IBD.
Dr. Loftus notes that leaving inflammation untreated can increase the risk of needing steroids, being hospitalized, having surgery, or even developing dysplasia or cancer. "The problem is that colonoscopy, CT and MR enterography are expensive and inconvenient tests, so you can't just repeat them every three months. So having a noninvasive, relatively inexpensive way to gauge the degree of inflammation would be ideal."
Fecal calprotectin (FC) has recently emerged as a promising noninvasive biomarker for assessing disease activity in UC. Calprotectin is a protein released by activated neutrophils during inflammation. Dr. Loftus and colleagues have reviewed the published literature examining FC as an inflammatory biomarker. And they noted that multiple systematic reviews and meta-analyses of inflammatory biomarkers have shown that FC is easily quantified in stool samples and has demonstrated a good correlation with the UC endoscopic inflammatory score, a measurement of endoscopic severity in UC. However, they also noted that the results had inconsistencies, with considerable heterogeneity in study populations, endoscopic activity scores, clinical end points, cutoff values and assay methods.
To further examine FC's potential as a biomarker for disease activity in UC, Dr. Loftus and colleagues conducted a retrospective observation study. With this study, they sought to establish the optimal FC assay cutoff values required to distinguish between Mayo endoscopic subscores (MES), to evaluate the diagnostic performance of those cutoffs, and to assess the correlation between FC and MES of patients diagnosed with UC. The results of this study were published in Inflammatory Bowel Diseases in 2024.
Study methods
Dr. Loftus and co-authors reviewed the electronic medical records of 177 adult patients with UC evaluated at Mayo Clinic in Rochester, Minnesota, from January 2017 to March 2023. They obtained clinical data and FC levels collected within 30 days before colonoscopy or flexible sigmoidoscopy. Three independent inflammatory bowel disease specialist endoscopists blindly reviewed the most severe endoscopic images for grading MES.
Results and conclusions
"Our study demonstrated a high, statistically significant correlation between FC levels and the endoscopy subscore. We were also able to establish cutoffs that were pretty predictive of endoscopy subscores."
Dr. Loftus and co-authors explain that this study suggests that FC can serve as a reliable, highly sensitive marker of endoscopic inflammation.
"Our study demonstrated a high, statistically significant correlation between FC levels and the endoscopy subscore," says Dr. Loftus. "We were also able to establish cutoffs that were pretty predictive of endoscopy subscores."
- An FC cutoff of 60 mcg/g effectively distinguished an MES of 0 from an MES of 1 to 3 and predicted clinical remission.
- An FC cutoff of 110 mcg/g effectively differentiated an MES of 0 to 1 from an MES of 2 to 3.
- An FC cutoff of 310 mcg/g distinguished an MES of 0 to 2 from an MES of 3.
"In summary, we can use the FC value to estimate the endoscopic subscore and make treatment decisions accordingly," explains Dr. Loftus. "This doesn't mean that FC replaces colonoscopy. We are still going to want to do that annually or so. But we could use serial FC measurements over the course of a year, perhaps every 3 to 6 months, and make adjustments as needed."
For more information
Suttichaimongkol T, et al. Diagnostic performance of a fecal calprotectin assay as a biomarker for Mayo endoscopic subscore in ulcerative colitis: Result from a tertiary referral center. Inflammatory Bowel Diseases. In press.
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