Background: Disease flares and hospitalisations have been associated to the need for surgery in patients with Crohn's disease (CD). Endoscopically evident intestinal inflammation one year after diagnosis has been associated with poorer outcomes while a “top down” therapy has been shown to be more beneficial than a step-up approach. Assessing for mucosal healing endoscopically may not be feasible though in daily, routine practice while further evidence is required to support the argument that treating to target alters the disease course. In this study, we aimed to test the hypothesis that ongoing intestinal inflammation as measured by the non-invasive biomarker faecal calprotectin (FCAL) is associated with surgical resection in CD.
Methods: From a large IBD cohort of patients currently under follow up at King's College Hospital, London, UK, we identified all the CD patients who were diagnosed locally and had serial FCAL in the context of their routine care (at routine appointments and during flare-ups). Utilising prospectively kept electronic patient records we identified 20 patients, meeting these monitoring criteria, who required a bowel resection for CD ≥12 months after diagnosis (cases) and matched them in a 1:2 ratio with controls based on disease duration. Flares were identified based on the physician assessment and endoscopic or radiologic findings. Continuous variables are summarised as medians followed by interquartile range. The Fisher exact test was used to compare categorical variables, the Mann-Whitney test for continuous variables and the ROC curve for diagnostic analysis.
Results: Median time to surgery was 9.5 years (8, 11) [control group follow up: 8 (7, 10), p=0.28]. Right hemicolectomy was the commonest procedure (14, 70%) followed by panproctocolectomy (2, 10%), small bowel resection (2, 10%) and stricturoplasty (2, 10%). Cases and controls did not differ in clinical characteristics or anti-TNF use. Flares and hospitalisations were more common in the cases group [20 (100%) vs. 23 (56%), p=0.0005 and 19 (95%) vs. 19 (48%) p=0.0002, respectively]. The baseline median FCAL, between flares, was 348 (240, 656) in cases and 92 (52, 164) in controls (p<0.001). When measured at 1 year after diagnosis the FCAL (FCAL1) was 549 (52, 1115) and 68 (26, 184) respectively (p<0.001). The area under the curve for FCAL1 to predict surgery was 0.83, 95% CI (0.73, 0.95) while a cut off at 600μg/g provided the highest likelihood ratio [18 (15, 69)].
Conclusions: Persistent intestinal inflammation is associated with flares, hospitalisations and surgery. Our results suggest that controlling intestinal inflammation in CD may alter the natural course of the disease. FCAL performed one year after diagnosis may identify high risk patients.