Objectives: To examine risk factors for non-frailty rheumatoid arthritis (RA) patients progressing to frailty.

Methods: A total of 304 RA patients with records for frailty assessment based on the Japanese Cardiovascular Health Study (J-CHS) criteria from 2020 to 2024 were included. Patients classified as non-frail (J-CHS scores 0-3) in 2020 were followed annually, and those who did and did not progress to frailty were categorized into the frailty progression (n = 100) and non-frailty progression (n = 204) groups, respectively. Risk factors for frailty progression were analyzed using the Cox proportional hazards model. Changes in DAS28-ESR and HAQ-DI between baseline and frailty progression were compared using a paired t-test.

Results: Compared to the non-frailty progression group, the frailty progression group was older (62.9 vs. 68.5 years) and had a longer duration of disease (9.1 vs. 14.2 years), lower methotrexate (MTX) use (74.4% vs. 56.1%), higher mean DAS28-ESR (2.40 vs. 2.77), and higher HAQ-DI (0.17 vs. 0.45). Both groups had high biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) use rates (34.3% vs. 42.0%). Risk factors for frailty events included age ≥ 65 years (HR 1.86), duration of disease ≥ 10 years (HR 1.64), DAS28-ESR < 2.6 (HR 0.64), HAQ-DI ≤ 0.5 (HR 0.45), and MTX use (HR 0.63). DAS28-ESR remained at a low disease activity level (baseline vs. frailty progression: 2.77 vs. 2.90), whereas HAQ-DI worsened at frailty progression compared to baseline (0.45 vs. 0.66).

Conclusions: Optimizing MTX use and achieving DAS/HAQ remission are crucial for preventing frailty. Non-medication-based approaches are also essential.