All-cause and cause-specific mortality in inflammatory bowel disease across the biologic era: a population-based matched cohort study

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is associated with increased mortality, but whether death rates and causes of death have changed across the biologic era is unclear. We aimed to assess all-cause and cause-specific mortality in Crohn's disease (CD) and ulcerative colitis (UC) across therapeutic eras. METHODS: We conducted a retrospective, population-based matched cohort study (1984-2019). IBD cases were matched 1:10 to unaffected controls by age, sex, and geography. Follow-up was stratified into a pre-biologic era (1984-2000) and biologic era (2001-2019). All-cause mortality was assessed using Cox models and cause-specific mortality using competing-risk methods. RESULTS: We identified 13 306 patients with IBD (5955 CD; 7351 UC) and 133 060 matched controls. During follow-up, 2156 patients with IBD (16.2%) and 19 095 controls (14.4%) died. CD was associated with higher all-cause mortality than controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.19-1.37). UC mortality did not differ from controls (HR 1.03, 95% CI 0.97-1.10). In era-stratified analyses, mortality was comparable in the pre-biologic era (IBD HR 1.04, 95% CI 0.93-1.15). In the biologic era, excess mortality was observed in CD (HR 1.34, 95% CI 1.24-1.45) but not in UC (HR 1.05, 95% CI 0.98-1.12). Compared with controls, CD had higher mortality from colorectal cancer (HR 2.28), renal disease (HR 2.79), non-Hodgkin lymphoma (HR 1.89), and sepsis (HR 2.12), while UC had higher mortality from colorectal cancer (HR 1.56) and cholangiocarcinoma (HR 3.21). CONCLUSIONS: All-cause mortality was modestly higher in CD, while UC mortality was similar to matched controls. The CD mortality gap appeared most evident with longer follow-up.