Faecal calprotectin in monitoring disease activity and risk of neoplasia in inflammatory bowel disease

Due to the increasing number of patients with inflammatory bowel disease (IBD), self-monitoring is being implemented for the treatment and follow-up of the patients. Faecal calprotectin (FC) has replaced repeated colonoscopies in evaluating the inflammatory activity, and also other faecal markers as faecal lactoferrin (FLf) are studied. An enzyme-linked immunosorbent assay (ELISA) test for FC is time-consuming, and several rapid point-of-care -tests have been developed. Long-standing mucosal inflammation of the colon predisposes to colonic dysplasia and colorectal carcinoma (CRC). The aims of this thesis were to evaluate the FC and FLf rapid tests in assessing the activity of colonic IBD, to develop a simple activity index for colonic IBD, to evaluate a new home-monitoring strategy in the follow-up and treatment of patients with colonic IBD, and to study the role of sequential FC measurements and the long-term inflammatory burden in predicting colonic dysplasia or CRC in UC patients. All patients were recruited from Helsinki University Hospital Clinic of gastroenterology. The inflammatory activity was assessed with clinical and endoscopic indices. The point-of-care faecal tests used were CerTest Calprotectin and Prevent ID CalDetect for FC, and CerTest Lactoferrin for FLf. For evaluatingand validating the FC and FLf rapid tests against the clinical, endoscopic, and histological inflammatory activity of colonic IBD, and for developing a combination activity index of FC and a symptom score, consecutive patients with colonic IBD referred to ileocolonoscopy from January 2013 to September 2013 were recruited. The final cohort comprised 72 patients. All patients provided a stool sample for FC and FLf. For the home-monitoring study, consecutive patients with colonic IBD between April 2015 and December 2016 were recruited and randomized into the home-monitoring and control patients. The final cohort constituted of 63 patients in the home-monitoring group and 60 patients in the control group, and the study period was 12 months for each patient. The clinical IBD activity and the health-related quality of life were assessed. The home-monitoring group performed a rapid FC test at home once in two months. For evaluating the role of FC in predicting dysplasia and IBD-related CRC, all the faecal samples and patients with a diagnosis of UC from January 2007 to December 2017 were collected from the databases. The final cohort was 4649 FC results from 982 UC patients. The histological grade of inflammation, detected dysplasias, sporadic adenomas, UC-associated colonic carcinomas, and colectomies related to UC were analyzed. In all studies, the inflammatory activity of IBD was low. The overall correlation with ELISA FC and rapid FC and FLf tests was statistically significant, but the tests yielded same results in only 53-76 % of samples. The patient-reported symptoms correlated significantly with FC, the histological inflammation activity in both CD and UC, and the clinical and endoscopic activity in UC but not in CD. The influence of IBD in the daily life of patients did not correlate with the IBD activity measured with more objective parameters. The combination index consisting of IBD symptom index and CalDetect test detected histological remission or mild disease slightly better than CalDetect test or patient-reported symptoms alone. In the home-monitoring study the drop-out rate was 71 % in total, 62 % in the home-monitoring group and 80 % in the control patients. Older patients and patients with higher disease burden were more compliant to the study. There were no differences in the IBD activity in the home-monitoring group between the baseline and the end of the study, or between the groups. 4 % of patients had IBD-associated dysplasia and 0.7 % developed CRC during a median follow up of 8 years. The colonic dysplasia or CRC was significantly more common in patients with constant severe inflammation and long-term histological inflammation than in patients with constant remission. FC or time-weighted FC did not predict dysplasia in the whole cohort. Both FC rapid tests and FLf test could identify patients with inactive IBD or non-inflammatory symptoms, and thus they can be used in screening for gastrointestinal inflammation. The patient-reported symptoms correlated well with the objective markers of IBD activity, while the quality of life did not. The self-monitoring of IBD activity provides an option for individualized care for IBD patients, but the adherence to the self-monitoring program remains a challenge. UC-patients with long-term severe inflammation are at higher risk for developing colonic dysplasia or IBD-related CRC than patients with long-term remission or mildly active disease. FC does not, however, predict the risk of dysplasia in unselected UC patients.