The sensitivity of fecal calprotectin in predicting deep remission in ulcerative colitis

Abstract

Background: Mucosal healing is proposed as treat-to-target in ulcerative colitis (UC), even though the definition of mucosal healing remains contested as it has been suggested to be assessed by either endoscopy, histology or both. However, all definitions require an endoscopic evaluation of the mucosa. As endoscopies are invasive and uncomfortable to the patient we aimed to calibrate noninvasive predictors of mucosal inflammatory status defined by both endoscopy and histology.

Methods: UC patients (n = 106) undergoing a sigmoid-/colonoscopy were prospectively included. Feces (fecal calprotectin, FC), blood samples (hemoglobin, C-reactive protein, orosomucoid, erythrocyte sedimentation rate, albumin) and symptom scores (Simple Clinical Colitis Activity Index, SSCAI) were collected and analyzed. The colonic mucosa was assessed by the Mayo endoscopic sub score and biopsies were obtained for a histologic grading by Geboes score. Predictive cutoff values were analyzed by receiver operating characteristics (ROC). A combined endoscopic and histologic assessment defined deep remission (Mayo =0 and Geboes ≤1) and activity (Mayo ≥2 and Geboes >3).

Results: Only FC showed a significant ROC curve (p < .05). We suggest FC (mg/kg) cutoffs for detection of following: Deep remission: FC ≤25; Indeterminate: FC 25-230 – an endoscopy is recommended if a comprehensive status of both endoscopic and histologic assessed activity is needed; Active disease: FC >230. The complete ROC data is presented, enabling extraction of an FC cutoff value’s sensitivity and specificity.

Conclusions: FC predicts endoscopic and histologic assessed deep remission and inflammatory activity of colon mucosa. Neither the markers in blood nor the SCCAI performed significant ROC results.

Keywords:

• Ulcerative colitis
• mucosal healing
• endoscopy
• histology
• fecal calprotectin
• predictive value

Acknowledgments

The authors thank the endoscopic section at Herlev and Gentofte Hospital University of Copenhagen for supporting the study and Hanne Fuglsang and Vibeke Voxen, Department of Gastro Laboratory, Herlev and Gentofte Hospital University of Copenhagen Hospital, for handling the analyses of fecal calprotectin. We also want to thank Marian Remijn and Renate Meyer at Department of Gastroenterology, University Hospital of North Norway, Tromsø, Norway for expert technical assistance.

Disclosure statement

Katrine Carlsen: MSD research grant; Tillotts pharma research grant.

Pia Munkholm: Research grant, advisory board: Tillotts, Takeda, Ferring; Calpro, North Zealand University Hospital grant.

Vibeke Wewer: MSD research grant; Tillotts pharma research grant.

Additional information

Funding

This work was supported by CALPRO A/S Norway, Tillotts Pharma Denmark, Capital Region Denmark, Herlev and Gentofte Hospital Research Foundation, Denmark and Foundation of Gastroenterology, University Hospital of North Norway, Tromsø, Norway.