The fecal concentration of calprotectin can be used to monitor for recurrence of Crohn’s disease, with a high enough negative predictive value that physicians can be confident they won’t miss patients with recurrent disease, researchers report in the May issue of Gastroenterology.
Approximately 80% of patients with Crohn’s disease require surgery during their lifetime—70% of these patients ultimately undergo a second surgery. Without treatment, 65%–90% of patients have endoscopic evidence of recurrence within 12 months.
Early detection of recurrence allows for treatment adjustments before symptoms relapse. Ileocolonoscopy is the standard for detecting disease recurrence, but this procedure is expensive, invasive, and inconvenient. Noninvasive tests for biomarkers are therefore needed to monitor post-operative endoscopic recurrence (see figure).
Calprotectin is a member of the S100 family of calcium-binding proteins. Its levels increase in all body fluids with degree of inflammation. Calprotectin can be quantified in feces using an ELISA.
Fecal concentration of calprotectin can detect Crohn’s disease activity with higher levels of sensitivity than other markers of inflammation, and is a reliable marker of mucosal healing. However, it was not clear whether it could identify patients with disease recurrence after surgery.
Emily K. Wright et al performed a prospective study to determine whether fecal concentration of calprotectin is a marker of recurrent mucosal lesions in the neoterminal ileum and anastomosis.
They analyzed levels of fecal calprotectin, serum levels of C-reactive protein, and Crohn’s disease activity index (CDAI) scores in 135 patients before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn’s disease. Ileocolonoscopies were performed 6 months after surgery for 90 patients, and 18 months after surgery for all patients.
Wright et al found that the median fecal calprotectin level decreased from 1347 μg/g before surgery to 166 μg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 μg/g).
Combined 6- and 18-month levels of fecal calprotectin correlated with the presence and severity of Crohn’s disease recurrence, whereas levels of C-reactive protein and CDAI scores did not. Levels of fecal calprotectin greater than 100 μg/g identified patients with endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value of 91%. This means that colonoscopy could have been avoided in 47% of patients.
Six months after surgery, a level of fecal calprotectin less than 51 μg/g in a patient in endoscopic remission indicated that s/he would maintain remission (negative predictive value, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, levels of fecal calprotectin decreased from 324 μg/g at 6 months to 180 μg/g at 12 months and 109 μg/g at 18 months.
In an editorial that accompanies the article, Alain M. Schoepfer and James D. Lewis explain that the role of fecal calprotectin in assessing post-operative recurrence has been debated because of inconsistent results in mainly small studies. The strengths of the study of Wright et al include its large size, prospective design, endoscopic validation, and longitudinal inter-individual measurements of fecal calprotectin.
Tests for biomarkers such as fecal calprotectin can be repeated more frequently than colonoscopies. This advantage could overcome the lower levels of sensitivity with which single measurements of biomarkers detect recurrence. Schoepfer and Lewis say that studies are needed to determine the optimal frequency for measuring fecal calprotectin.
However, they conclude that measurement of fecal calprotecin could have an important role in monitoring Crohn’s disease recurrence after intestinal resection; it is clearly superior to measurement of c-reactive protein or CDAI score.
Schoepfer and Lewis propose that an algorithm to help physicians decide whether to measure fecal calprotectin or perform colonoscopy, based on patient characteristics, could improve the cost effectiveness and feasibility of post-operative testing.
This article has continuing medical education activity.