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Background: Exercise may reduce health complications related to early rheumatoid arthritis (RA), thereby contributing to an improved prognosis. Advances in RA research support a “window of opportunity” in early disease phases, during which non-pharmacological strategies such as exercise may be particularly beneficial [1–3]. However, no previous review has systematically evaluated the effects of exercise-based interventions in pre-clinical and early RA.
Objectives: This systematic review and meta-analysis aimed to assess the effectiveness of exercise-based interventions in pre-clinical and early RA phases and to identify which intervention characteristics are associated with better clinical outcomes.
Methods: We searched PubMed/MEDLINE, Scopus, and Web of Science up to July 2025 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. Random-effects meta-analyses, meta-regressions, and RoB 2 risk-of-bias assessments were conducted.
Results: Fifteen studies involving 1,154 participants with early RA (≤0.5 to <5 years disease duration) were identified. Most studies showed moderate-to-high risk of bias. No randomized trials were identified in asymptomatic or at-risk (pre-clinical) populations. Exercise improved hand status (ES=0.33 [95%CI: 0.10 to 0.57], p=0.001), self-reported functional capacity (ES=0.36 [95%CI: 0.00 to 0.73], p=0.049), muscle strength (ES=0.66 [95%CI: 0.16 to 1.15], p=0.022), and pain (ES=0.66 [95% CI: 0.00 to 1.22], p=0.049). No effects appeared for disease activity (ES=0.17 [95%CI: −0.05 to 0.40], p=0.101), morning stiffness (ES=0.13 [95%CI: −0.25 to 0.52], p=0.351), test-based functional capacity (ES = 0.38 [95%CI: −0.12 to 0.89], p=0.112), and quality of life (ES=0.42 [95% CI:−0.18 to 1.02], p=0.134). However, sensitivity analyses revealed benefits for test-based functional capacity (ES=0.19 [95%CI: 0.00 to 0.37], p=0.047) and morning stiffness (ES=0.27 [95%CI: 0.08 to 0.46); p=0.024). Meta-regression showed no moderating influence of disease duration, intervention type, or supervision (p≥0.089).
Conclusions: Exercise is safe and confers modest benefits in muscle strength, hand function, functional capacity, pain, and morning stiffness in early RA, supporting its integration alongside pharmacological care, in line with current EULAR and ACR recommendations [4–6]. Major evidence gaps remain for cardiovascular fitness, fatigue, mental health, inflammatory biomarkers, and pre-clinical or at-risk populations, highlighting the need for well-designed preventive and early-phase trials.
REFERENCES: [1] Klareskog L, Alfredsson L. Prevention vs treatment of rheumatoid arthritis. Immunother Adv 2023;3:1–6.
[2] Mankia K, Siddle HJ, Kerschbaumer A, Alpizar Rodriguez D, Catrina AI, Cañete JD, et al. EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis. Ann Rheum Dis 2021;80:1286–98.
[3] O’Neil LJ, Alpízar-Rodríguez D, Deane KD. Rheumatoid Arthritis: The Continuum of Disease and Strategies for Prediction, Early Intervention, and Prevention. J Rheumatol 2024;51:337–49.
[4] American College of Rheumatology. 2022 American College of Rheumatology (ACR) guideline forexercise, rehabilitation, diet, and additional integrative interventions for rheumatoid arthritis. Empower Rheumatol Prof to Excel Their Spec 2023.
[5] Combe B, Landewe R, Daien CI, Hua C, Aletaha D, Álvaro-Gracia JM, et al. 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis 2017;76:948–59.
[6] Rausch Osthoff AK, Niedermann K, Braun J, Adams J, Brodin N, Dagfinrud H, et al. 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Ann Rheum Dis 2018;77:1251–60.
Acknowledgments: NIL.
Disclosure of Interests: None declared.