Effects of exercise interventions on clinical outcomes in pre-clinical and early rheumatoid arthritis: a systematic review and meta-analysis

BACKGROUND: Exercise reduces health complications related to early rheumatoid arthritis (RA). No previous review has systematically evaluated the effects of exercise in pre-clinical and early RA. OBJECTIVE: This systematic review and meta-analysis aimed to assess the effectiveness of exercise in pre-clinical and early RA and to identify which intervention characteristics are associated with better clinical outcomes. METHODS: We searched PubMed/MEDLINE, Scopus, and Web of Science up to January 2026 for randomized controlled trials examining effects of exercise in pre-clinical and early RA on: (i) inflammation markers and disease activity, (ii) muscle strength, cardiovascular fitness, functional capacity, and body composition, and (iii) pain, fatigue and quality of life. Effect sizes (ES) with 95% confidence intervals (95% CI) were calculated using random-effects meta-analyses. Meta-regressions and RoB 2 risk-of-bias assessments were conducted. RESULTS: Fifteen studies involving 1154 participants with early RA were identified. Most studies showed a moderate-to-high risk of bias. No randomized trials were identified in pre-clinical populations. Exercise improved hand status (ES = 0.33; 95% CI, 0.10-0.57; P = 0.001), self-reported functional capacity (ES = 0.36; 95% CI, 0.00-0.73; P = 0.049), muscle strength (ES = 0.66; 95% CI, 0.16-1.15; P = 0.022), and pain (ES = 0.66; 95% CI, 0.00-1.22; P = 0.049). No effects appeared for disease activity (ES = 0.17; 95% CI, -0.05-0.40; P = 0.101), morning stiffness (ES = 0.13; 95% CI, -0.25-0.52; P = 0.351), test-based functional capacity (ES = 0.38; 95% CI, -0.12-0.89; P = 0.112), and quality of life (ES = 0.42; 95% CI, -0.18-1.02; P = 0.134). Sensitivity analyses revealed benefits for test-based functional capacity (P = 0.047) and morning stiffness (P = 0.024). Meta-regression showed no moderating effect of disease duration, intervention type, or supervision (P ≥ 0.089). CONCLUSIONS: Exercise confers modest benefits in strength, hand function, functional capacity, pain, and morning stiffness in early RA, supporting its integration alongside pharmacologic care. Major evidence gaps remain for cardiovascular fitness, fatigue, mental health, inflammation, and the pre-clinical population. Well-designed preventive and early-phase trials are needed. TRIAL REGISTRATION: PROSPERO identifier: CRD42024522163.