Fecal calprotectin (FP) levels indicate mucosal healing in patients with ulcerative colitis (UC), but are too variable for this biomarker to reliably replace endoscopy and biopsy, according to a report published in the November issue of Clinical Gastroenterology and Hepatology.
FP is a complex of two calcium-binding proteins, and the level is used clinically to detect increased inflammation of the intestines. Although not diagnostic for UC, FP is used to rule out noninflammatory conditions, to identify patients requiring endoscopy and biopsy, to predict relapse, and to monitor response to drugs (tumor necrosis factor antagonists and steroids).
Measurement of FP may be useful in assessing mucosal healing, which is the goal of treatment. At this time, the Mayo Endoscopic Score (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) index are used to assess mucosal healing, but endoscopy is invasive and is associated with complications. In addition, mucosal inflammation that is so mild that it is not detected with endoscopy may nevertheless precede relapse. Therefore, the researchers considered the role of FP testing in evaluating patients for endoscopy.
Klaus Theede, MD, from the Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark, and colleagues conducted an observational cross-sectional study of 120 patients to evaluate the utility of using FP level to indicate mucosal healing. The investigation considered both MES and UCEIS scores, clinical extent of disease (partial Mayo score), and histologic inflammatory activity score (modified Harpaz Index).
The results revealed "an increasing concentration of FC with increasing grade of clinical disease activity (P < .0001)." The researchers established a cutoff level for FC of 192 mg/kg for predicting endoscopic mucosal healing (based on MES and UCEIS scores), with positive predictive values of 0.71 (95% confidence interval [CI], 0.45 - 0.87) and 0.65 (95% CI, 0.42 - 0.83), respectively, and negative predictive values of 0.90 (95% CI, 0.87 - 1.00) and 0.93 (95% CI, 0.90 - 1.00), respectively. This level was comparable to that for complete clinical remission, according to the partial Mayo score of 0, but is considerably lower than the 415 mg/kg used to indicate "near-complete" clinical remission (partial Mayo score of less than or equal to 2).
A cutoff FC level of 171 mg/kg applied to patients who had histologic evidence of mucosal healing, with a positive predictive value of 0.75 (95% CI, 0.50 - 0.89) and a negative predictive value of 0.90 (95% CI, 0.87 - 0.99). All four measures (FC, MES, UCEIS, and histologic inflammatory activity) were in sync, with higher levels reflecting more extensive pathology.
The study had several limitations. It did not follow patients longitudinally and so did not assess prognostic value of FC as a biomarker. The single stool sample and FC measurements per patient did not account for intraindividual variation, which can be as great as 39%. The only version of endoscopy that all patients received was flexible sigmoidoscopy. The nonuniform procedures hampered the ability to distinguish pancolitis from left-sided colitis. The researchers conclude that FC can predict mucosal and histological healing and is a marker for mucosal inflammation in UC, but is at present too variable to replace endoscopic exam and biopsy.
"Theede et al report the FC results of 120 UC patients that required sigmoidoscopy because of disease flare or cancer surveillance. The latter group is likely to have quiescent disease. This means that the researchers compared FC levels in preselected patient groups at both ends of the disease-activity spectrum," Patrick van Rheenen, MD, PhD, a pediatric gastroenterologist at University Medical Center Groningen, the Netherlands, told Medscape Medical News.
"Inclusion of these categories of patients causes overestimation of the value of FC relative to the practical situation, where a test is necessary to discriminate between those who have preclinical relapse and those with quiescent UC. Theede et al have shown that the FC test can identify UC patients with mucosal healing under ideal circumstances, but a study that evaluates whether FC can discriminate in routine practice is yet to be performed."
Grants from AbbVie and Ferring Pharmaceuticals supported this research. Dr Theede is on the advisory board of AbbVie and has been an invited speaker for that company and for MSD. The other authors and Dr van Rheenen have disclosed no relevant financial relationships.
Clin Gastroenterol Hepatol. Published online June 4, 2015. Abstract
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Cite this: Fecal Calprotectin Identifies Healing in Ulcerative Colitis - Medscape - Nov 06, 2015.