Rheumatoid arthritis and risk of gallstone disease: a nation-wide population-based study

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with systemic inflammation and various comorbidities, including potential gallbladder disease. However, evidence linking RA to gallstones or cholecystectomy remains limited and inconsistent. This study assesses whether patients with RA are at higher risk of developing gallstones and undergoing cholecystectomy than individuals without RA.

Using data from the Korean National Health Insurance Service, we identified 54,910 individuals diagnosed with RA between 2010 and 2017. After applying separate exclusion criteria for the analyses of developing gallstones and undergoing cholecystectomy, we matched those patients in a 1:3 ratio based on age and sex to derive a control population without RA. The study participants were followed from 1 year after their RA diagnosis or corresponding index date (lag period) to Dec. 31, 2020. Cox regression analyses were performed to estimate hazard ratios of developing gallstones and undergoing cholecystectomy compared with the matched controls.

We analyzed 46,523 patients with RA and 139,569 matched controls, with a follow-up period ranging from 3.5 to 7.3 years. During the follow-up, gallstone disease developed in 8.33% of patients with RA and 5.51% of the matched controls, corresponding to incidence rates of 15.69 and 10.09 per 1,000 person-years, respectively. The risk of incident gallstones was higher in the RA cohort than in the matched control group [adjusted hazard ratio (aHR) 1.58; 95% confidence interval (CI): 1.52-1.65, P<0.001]. During the same period, 1.24 % of patients with RA and 1.1% of the matched control group underwent cholecystectomy, for incidence rates of 2.27 and 2.0 per 1,000 person-years, respectively. Patients with RA appear to have a marginally elevated risk of undergoing cholecystectomy, compared with matched controls (aHR 1.15, 95% CI 1.05-1.27, P=0.04).

The risk of gallstone disease is higher in individuals with RA than in matched controls.