Multimorbidity and risk of infection in patients with rheumatoid arthritis: Population-based case-control study

Patients with rheumatoid arthritis (RA) have elevated infection risk owing to disease- and treatment-related immune dysfunction. Whether multimorbidity adds risk remains uncertain. This study evaluated the association between multimorbidity and infection in RA.

A nationwide nested case-control study was conducted in Korea using the Health Insurance Review and Assessment Service database mapped to the Observational Medical Outcomes Partnership Common Data Model. RA was identified by the International Classification of Diseases, 10th revision (M05-M06) with same-day disease-modifying antirheumatic drug prescriptions in 2018-2019. Patients with major immunodeficiencies or recent infections were excluded. Cases were the first serious, opportunistic, or herpes zoster infections between January 1, 2020, and April 30, 2022. Four controls were matched to each case by age, sex, and seropositivity. Multimorbidity was assessed using chronic conditions present during the 2 years preceding infection.

Compared with patients with <10 conditions, those with RA and ≥10 conditions had higher odds of infection. A dose-response pattern was evident across multimorbidity groups. Adjusted odds ratios were 1.44 (95% confidence interval 1.32-1.58) for serious infection, 2.19 (1.06-4.53) for opportunistic infection, and 1.18 (1.05-1.34) for herpes zoster. Associations were consistent across subgroups. Multimorbidity increased nonfatal but not fatal infections. Among major infection types, only complicated skin and soft tissue infections were significant.

In Korean adults with RA, multimorbidity substantially increases infection risk in a dose-response manner, particularly for cutaneous and nonfatal infections. These results highlight the cumulative impact of chronic conditions and support holistic management with proactive infection monitoring.