All-cause and cause-specific mortality in microscopic colitis: a Danish nationwide matched cohort study

Background The long-term natural history of microscopic colitis remains uncertain. Aim To describe the mortality in a large unselected cohort of patients with microscopic colitis. Methods All Danish patients above 18 years with an incident diagnosis of microscopic colitis from 2001 to 2018 were identified from nationwide registries and compared to age- and sex-matched controls (variable 1:10 ratio). Patients were categorised according to subtypes: lymphocytic colitis and collagenous colitis. The relative risk of death by any cause was analysed with Cox regression models estimating both crude and comorbidity-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Cause-specific death was evaluated with cumulative incidence functions. An E-value was calculated to address the impact of unmeasured confounding. Results The final cohort consisted of 14 024 patients with microscopic colitis. The mean follow-up was 5.8 (standard deviation SD, 2.9) years and the mean age at diagnosis was 61.1 (SD 13.9) years, 70% were women and 41% were diagnosed with lymphocytic colitis. The main results showed a 25% increased risk of all-cause death in patients with microscopic colitis; however, the relative risk was attenuated to 9% when adjusting for comorbidities (95% CI, 1.05-1.14). The E-value indicates that unmeasured confounding could explain the residual observed increased all-cause mortality. Mortality was significantly increased in patients with both lymphocytic colitis (HR 1.15; 95% CI, 1.08-1.23) and collagenous colitis (HR 1.06; 95% CI, 1.01-1.12) in fully adjusted analyses. The absolute difference in death between patients with microscopic colitis and matches was 0.9% at 1 year, 2.8% at 5 years, 5.0% at 10 years and 3.0% at 15 years. Cumulative incidence functions showed that patients with microscopic colitis were more likely to die due to smoking-related diseases including ischemic heart and lung diseases, but had a significant decreased risk of death due to colorectal cancers (P < 0.0001). Conclusion In an unselected large nationwide cohort of patients with microscopic colitis, the risk of death was significantly increased compared to the background population. However, the increased mortality seemed to be associated to a high burden of comorbidities and unmeasured life-style factors including smoking and not microscopic colitis per se.