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

Introduction: 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.

Methods: We utilized a longitudinal RA cohort established at the VA Puget Sound Health Care System. RA disease activity (DAS28-CRP) and frailty (measured by the Fried Frailty Phenotype (FFP)) were evaluated at baseline and at 1-year. Frailty was categorized as robust, pre-frail or frail. Ordinal logistic regressions assessed the cross-sectional associations of DAS28-CRP and frailty at baseline and at 1-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, csDMARD and bDMARD use.

Results: 132 patients with RA aged 64.2±11.3 years were included, with 73% male (73%) and 69% White, 11% Black, and 12% reports multiple races. Mean baseline DAS28-CRP was 3.9±1.3 and 35 (27%) were robust, 77 (58%) prefrail, and 20 (15%) frail. DAS28-CRP (per 1 unit increase) was associated with higher FFP category at baseline (aOR: 1.98, p<0.0001). Disease activity increased in those whose frailty score worsened at 1 year (change score: 0.61±0.96, p=0.0121). Increased DAS28-CRP was independently associated with a higher frailty category over one year (aOR: 3.31, p<0.0001, N=65).

Conclusion: 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.