Risk of tuberculosis disease among patients with inflammatory bowel disease and inflammatory rheumatic disease treated with biologics in Denmark: a nationwide cohort study.

Objectives: This nationwide retrospective cohort study estimates TB disease risk in adults and children with inflammatory bowel disease (IBD) and inflammatory rheumatic disease (IRD) treated with immunosuppressive biologics in Denmark, including temporal trends and risk stratification by TB infection status and country of birth.

Methods: Patients diagnosed with IBD or IRD between 1994 and 2018 were identified using the Danish National Patient Registry. Treatments with biologics and diagnoses of TB disease were determined through ICD-10 codes and microbiological records. Patient demographics, interferon-gamma release assay (IGRA) results, and drug use data were collected from national databases. Poisson regression was used to calculate TB incidence rates (IR) and assess associations with biologic treatment, IGRA-status, country of birth, age, and sex.

Results: During 553,551 person-years of follow-up (PYFU), 117 patients with TB disease were identified, with 71 cases occurring in biologic-naïve patients and 46 in biologic treated individuals. The crude IR was 39.3/100,000 PY (95% CI 29.4-52.4) for biologic treated individuals, compared to 12.4/100,000 PY (95% CI 9.2-16.8) for naive patients, yielding an incidence rate ratio (IRR) of 3.2 (95%CI 2.0-4.9). The TB risk was higher in IGRA-positive patients (vs. negative, IRR 45.0, 95% CI 12.0-168.2) and those born in intermediate (vs. low incidence country, IRR 7.9, 95% CI 3.3-18.9) or high TB-incidence countries (vs. low incidence country, IRR 7.5, 95% CI 2.9-19.1).

Conclusion: The elevated risk of TB disease in patients with IRD and IBD treated with biologics is strongly associated with IGRA positivity and country of birth. These findings highlight the importance of comprehensive baseline TB risk assessment, patient education in combination with personalized follow-up to guide preventive strategies in this population.