3 AC&R Study Summaries: RA & Frailty, Hydroxychloroquine Can Protect Kidneys in Lupus Nephritis, & PT for Knee OA

The Impact of RA Disease Activity on Frailty

By Hannah Brubeck, BS, Courtney Loecker, PhD MSN, & Katherine Wysham, MD

Why was this study done? Patients with rheumatoid arthritis (RA) experience frailty earlier and more frequently than the general population. Secondary frailty, in which frailty is driven by an uncontrolled underlying condition, has been demonstrated in other disease states but has yet to be explored in RA. There is an established cross-sectional relationship between RA disease activity and frailty, but it is unclear whether this relationship persists longitudinally or provides evidence for secondary frailty. We evaluated the association of disease activity with frailty in a longitudinal RA cohort.

What were the study methods? Participants were veterans who were enrolled in the RA, Frailty and Osteoporosis (FROst) Repository in the VA Puget Sound Health Care System. The study outcome was phenotypic frailty, which measures exhaustion, weight loss, physical activity, walk speed and grip strength. We used ordinal logistic regression models to assess the cross-sectional relationship between RA disease activity (DAS28-CRP) and frailty. We used paired T-tests and mixed ordinal regression models to assess the longitudinal relationship between changes in disease activity and frailty over one year.

What were the key findings? Higher disease activity was cross-sectionally associated with higher frailty category at baseline (OR 1.98, P<0.0001). This finding was independent of important covariates, including age, RA duration and medication use. Nearly one-third of veterans had higher frailty scores after one year, and higher disease activity was independently associated with worsened frailty over time (OR 3.31, P<0.0001).

What were the main conclusions? Increasing RA disease activity is associated with frailty both cross-sectionally and longitudinally. This suggests that active RA disease may influence frailty measurement, potentially confounding frailty assessment, as well as contribute to frailty over time through cumulative inflammation and damage. Taken together, these findings support the concept of secondary frailty.

What are the implications for patients and clinicians? Clinicians should consider that active RA disease may confound frailty ascertainment and should be taken into consideration if frailty is being used to inform treatment decisions. Frailty measurement, therefore, should ideally be performed when RA disease is optimized. Our findings also support the ACR/EULAR recommended treat-to-target goals of low disease activity or remission, which may help mitigate or prevent frailty onset.

The study: Brubeck HF, Riggles KE, Bass RS, et al. Evaluating the longitudinal association of rheumatoid arthritis disease activity with phenotypic frailty: Evidence for secondary frailty? Arthritis Care Res (Hoboken). 2025 Jul 23. Epub ahead of print.