Mortality risk in IBD

January 13, 2026

Issue 01

Clinical Question

What is the mortality risk associated with histologic vs. clinical activity in IBD?

Editor’s Bottom Line

The small overall increases in mortality among patients with IBD may be related to disease activity, whether measured clinically or histologically.

Reference

Sun J, Mårild K, Bergman D, et al. Histologic remission and mortality in patients with inflammatory bowel disease: a nationwide cohort study. Clin Gastroenterol Hepatol. Epub ahead of print Nov 13, 2025. https://doi.org/10.1016/j.cgh.2025.10.030

Synopsis

To investigate differences in the impact of histologic and clinical activity on mortality risk in IBD patients, researchers conducted a nationwide cohort study in Sweden using national health registries. The study, which included histological data, examined 63,358 patients diagnosed with IBD between 1969 and 2017, revealing 106,418 periods of histologic inflammation and 49,174 periods of histologic remission. Another mutually non-exclusive group of 102,352 patients diagnosed between 1969 and 2020 had clinical activity data examined. In some cases, patients had both histologic and clinical disease activity data.

Histologic inflammation was defined by histopathology codes indicating ileocolorectal inflammation or ulceration/erosion, which the researchers assumed persisted for up to 12 months following biopsy. Clinical activity was defined as the presence of IBD-related surgery, hospitalization, corticosteroid use or initiation of immunomodulators/biologics. The primary outcome was all-cause mortality within two years, with cause-specific mortality examined for cardiovascular disease, malignancy, digestive diseases and infections.

For histologic inflammation vs. remission, the two-year all-cause mortality rate was 121 vs. 64.8 per 10,000 person-years, respectively (adjusted hazard ratio [aHR]: 1.45; 95% Confidence Interval [CI]: 1.30–1.61). This elevated risk was consistent across Crohn’s disease (aHR: 1.42), ulcerative colitis (aHR: 1.44) and unclassified IBD (aHR: 1.56). Histologic inflammation was associated with increased mortality from cardiovascular diseases (aHR: 1.48), malignant neoplasms (aHR: 1.26) and digestive diseases (aHR: 2.29).

Looking at patients with clinically quiescent IBD, the researchers found histologic inflammation was associated with a 42% increased risk of two-year mortality (aHR: 1.42; 95% CI: 1.08–1.87). The mortality risk persisted across all age groups, calendar periods and disease durations, including inflammation occurring more than five years after IBD diagnosis (aHR: 1.31).

For clinically active vs. quiescent disease, two-year mortality risk was also substantially higher, with a mortality rate of 352.6 vs. 106.3 per 10,000 person-years, respectively (aHR: 3.35; 95% CI: 3.21–3.49). Clinically active disease was associated with markedly elevated mortality from malignant neoplasms (aHR: 4.82), cardiovascular diseases (aHR: 2.54) and digestive diseases (aHR: 5.67). The higher mortality risk in this group was most pronounced immediately after IBD diagnosis (aHR: 8.78) but remained significant even for active disease occurring more than five years after diagnosis (aHR: 3.36).

Details

Study Design: Nationwide cohort study using Swedish health registries
Funding: Swedish Society for Medical Research, European Crohn’s and Colitis Organization, Swedish Society of Medicine, Ruth and Richard Julin Foundation, Karolinska Institutet
Allocation: Not applicable
Setting: Multicenter
Level of Evidence: 2b