Evaluating the Longitudinal Association of Rheumatoid Arthritis Disease Activity With Phenotypic Frailty: Evidence for Secondary Frailty?

Abstract

The cross-sectional association between rheumatoid arthritis (RA) disease activity and frailty has been described; however, the longitudinal relationship is less well understood. We evaluated the association between disease activity and frailty over time. We used a longitudinal RA cohort established at the Department of Veterans Affairs Puget Sound Health Care System. RA disease activity (Disease Activity Score in 28 joints using the C-reactive protein level [DAS28-CRP]) and frailty (measured by the Fried Frailty Phenotype [FFP]) were evaluated at baseline and at one year. Frailty was categorized as robust, prefrail, or frail. Ordinal logistic regressions assessed the cross-sectional associations of DAS28-CRP and frailty at baseline and at one year. Paired t-tests and multivariable mixed ordinal logistic regressions assessed the longitudinal associations of DAS28-CRP and frailty. Models were adjusted for age, sex, disease duration, prednisone use, conventional synthetic disease-modifying antirheumatic drug (DMARD) use, and biologic DMARD use. A total of 132 patients with RA aged 64.2 ± 11.3 years were included; 73% were male, 69% were White, 11% were Black, and 12% reported multiple races. The mean ± SD baseline DAS28-CRP was 3.9 ± 1.3, and frailty was categorized as robust in 35 (27%) patients, prefrail in 77 (58%) patients, and frail in 20 (15%) patients. DAS28-CRP (per 1-unit increase) was associated with a higher FFP category at baseline (adjusted odds ratio [aOR] 1.98, P < 0.0001). Disease activity increased in those whose frailty score worsened at one year (mean ± SD change score 0.61 ± 0.96, P = 0.0121). An increased DAS28-CRP was independently associated with a higher frailty category over one year (aOR 3.31, P < 0.0001; n = 65). Disease activity is independently associated with phenotypic frailty. Increased disease activity over time is associated with worsening frailty status. Future studies are needed to explore this longitudinal relationship and to determine if controlling disease activity can mitigate frailty.