Associations of Frailty With the Risk of Incident Cancer and Cancer-Related Mortality in Veterans With Rheumatoid Arthritis.

OBJECTIVE

This study investigated the association between frailty and cancer incidence and mortality in patients with rheumatoid arthritis (RA). It 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 Registry (2002-2023). Frailty status was categorized at baseline using the Veterans Affairs Frailty Index (VA-FI): robust (VA-FI <0.10), prefrail (VA-FI 0.11-0.20), and frail (VA-FI >0.20). Cancer incidence and cancer-related deaths were evaluated using competing risk models, adjusting for demographics, lifestyle factors (eg, smoking), RA characteristics (eg, seropositivity, Disease Activity Score-28), medication use, and comorbidities. We additionally studied domain-specific frailty exposures and linear frailty modeling 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 (prefrail), and 19.9 (frail). In fully adjusted models, prefrailty (subdistribution hazard ratio [sHR] 1.37, 95% confidence interval [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 (robust), 10.6 (prefrail), and 9.8 (frail) 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.