(SLA-167) Antibiotic use and risk of inflammatory bowel disease in older adults: a nationwide self-controlled case series study

Background: The incidence of inflammatory bowel disease (IBD) is rising, with antibiotics partly suspected as a contributing factor. Antibiotic use has been associated with IBD in early and mid-life, however data in older adults remain limited. Genetic confounding in cohort studies pose challenges from drawing conclusions from the existing literature.

Objectives: We aimed to investigate the risk of IBD in adults aged 65 years and older on and following antibiotics treatment.

Methods: A nationwide self-controlled case series study including adults aged ≥65 years with a new prescription of antibiotics, diagnosed with incident, biopsy-confirmed, IBD in Sweden, 2007–2017. We identified IBD-patients from the nationwide histopathology cohort ESPRESSO, with patients individually linked to several nationwide registers. We estimated the incidence rate ratio (IRR) of IBD with a conditional Poisson regression for four risk periods: on treatment, 1-14, 15-91 and 92-365-days post treatment, compared with the non-treatment periods in the same individual. Antibiotic duration was identified based on the prescribed daily dose. We also conducted a negative control outcome analysis where individuals with biopsy-confirmed normal mucosa were regarded as cases to test the association between gastrointestinal workup and antibiotic use. Finally, we computed E-values for quantitative bias assessment.

Results: We identified 3,766 persons with incident IBD (median age at diagnosis 73 years), of whom 50% were female. Compared with the non-treatment periods, the risk of IBD in the age-adjusted analysis increased on treatment (IRR: 2.2 [1.9 - 2.7], E-value: 3.9), 1-14 days (IRR: 2.0 [1.7 – 2.4], E-value: 3.4), 15-91 days (1.6 [1.5 – 1.8], E-value: 2.7) and 92-365 days post treatment (1.3 [1.2 - 1.4], E-value: 1.8). In the negative control outcome analysis, the risk of biopsy-confirmed normal mucosa was also increased after antibiotics use, yet with a slightly lower effect estimates than for IBD: on treatment (IRR: 1.6 [1.5 – 1.8], E-value: 2.6), 1-14 days (IRR: 1.8 [1.7 – 2.0], E-value: 3.1), 15-91 days (1.6 [1.5 – 1.6], E-value: 2.5) and 92-365 days post treatment (1.1 [1.1 - 1.2], E-value: 1.6)

Conclusions: In this nationwide study of Swedish adults aged ≥65 years, antibiotic use was associated with an increased risk of IBD, which gradually decreased over time after antibiotic exposure. However, negative control analyses indicated that a major portion of this observed risk may be attributable to heightened surveillance among patients receiving antibiotics. Clinically, these findings highlight the importance of careful antibiotic prescribing, balancing the need for treating infections with the potential risk of IBD.