Associations of Frailty with the Risk of Incident Cancer and Cancer-related Mortality in Veterans with Rheumatoid Arthritis.

Abstract

To investigate the association between frailty and cancer incidence and mortality in patients with rheumatoid arthritis (RA). The study aimed to identify how frailty influences cancer risk, and cancer-specific outcomes. This retrospective cohort study analyzed data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry (2002-2023). Frailty status was categorized at baseline using the Veterans Affairs Frailty Index (VAFI): robust (VAFI <0.10), pre-frail (VAFI 0.11-0.20), and frail (VAFI >0.20). Cancer incidence and cancer-related mortality were evaluated using competing risk models, adjusting for demographics, lifestyle factors (e.g., smoking), RA characteristics (e.g., seropositivity, Disease Activity Score-28), medication use, and comorbidities. We additionally studied domain-specific frailty exposures, and linear frailty modelling in sensitivity analyses. Results A total of 2,723 individuals met eligibility criteria (mean age: 63.8 ± 11.2 years; 87.6% male; 15.4% Black). Age-adjusted cancer incidence rates per 1,000 person-years were 12.3 (robust), 15.5 (pre-frail), and 19.9 (frail). In fully adjusted models, pre-frailty (sHR: 1.37, 95% CI: 1.02-1.84) and frailty (sHR: 1.83, 95% CI: 1.23-2.71) were significantly associated with higher cancer incidence. Cancer-related mortality rates were 7.8, 10.6, and 9.8 per 1,000 person-years, with no significant associations for overall frailty. Domain-specific and sensitivity analyses were consistent with these findings. Frailty was independently associated with increased cancer incidence in RA, suggesting frailty may help identify patients at higher risk for malignancy.