The Natural History of Crohn’s Disease Leading to Intestinal Failure: A Longitudinal Cohort Study from 1973 to 2018

Background and Aims: The natural history of Crohn’s disease leading to intestinal failure is not well characterised. This study aims to describe the clinical course of Crohn’s disease preceding intestinal failure, and compare disease activity and burden between Crohn’s disease patients with and without intestinal failure. Methods: Patients with Crohn’s disease complicated by intestinal failure from Rigshospitalet, Copenhagen (n=182) and a nationwide Danish Crohn’s disease cohort without intestinal failure (n=22,845) were included. Using nationwide medical and social registries in Denmark, disease activity was determined from hospitalisations, surgeries and outpatient medications, and disease burden was determined from employment and mortality data. Results: The 10-year cumulative incidence of intestinal failure following Crohn’s disease diagnosis declined from 2.7% prior to 1980 to 0.2% after 2000. Compared to Crohn’s disease patients without intestinal failure, those with intestinal failure experienced significantly longer duration of severe disease (50 vs. 19 years per 100 patient-years, p<0.01), secondary to greater corticosteroid use (71% vs. 60%, p =0.02), inpatient contacts (98% vs. 55%, p <0.01), and abdominal surgeries (99% vs. 48%, p <0.01). However, exposure to biologics was not different between the two groups (20.4% vs. 21%, p=0.95), and duration on biologics was shorter in Crohn’s disease patients with intestinal failure(2,068 vs. 4,126 days per 100 patient-years, p =0.02). Standard mortality ratio in Crohn’s disease patients with intestinal failurewas 3.66 [97.5% CI 2.79,4.72]. Conclusion: Patients with Crohn’s disease complicated by intestinal failure experienced a more persistently severe preceding course of Crohn’s disease, but were not more likely to be treated with biological therapy.