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

OBJECTIVE: 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. METHODS: 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. CONCLUSION: Frailty was independently associated with increased cancer incidence in RA, suggesting frailty may help identify patients at higher risk for malignancy.