#5-29E. Redefining the Window of Opportunity: Chronicity and Prevention in Rheumatoid Arthritis (Lancet Rheumatol, 2026)

Did you know that the biological onset of rheumatoid arthritis actually precedes the appearance of clinical arthritis by several years? This narrative review integrates temporal and tissue-integrated perspectives to trace the preclinical phases of RA, where asymptomatic autoimmunity and systemic inflammatory shifts gradually mature into subclinical joint inflammation. A crucial clinical revelation highlighted here is that early intervention with methotrexate offers a sustained, long-term reduction in rheumatoid arthritis development specifically within ACPA-negative patients, suggesting that the "window of opportunity" and biological checkpoints of chronicity are distinct from those of ACPA-positive trajectories. However, as we critically appraise this research, it is vital to acknowledge that prospective longitudinal data for the ACPA-negative pre-RA population are still scarce, meaning current models for this subgroup remain largely conceptual rather than evidence-based. For clinicians, this paper underscores the critical clinical need to move toward personalized, stage-specific preventive strategies based on a patient's ACPA status, allowing us to actively intercept disease progression before self-sustaining chronicity is irreversibly locked.

Citation: Alper Cevirgel and Annette H. M. van der Helm-van Mil. When and how chronicity develops in rheumatoid arthritis: towards a temporal and tissue-integrated perspective. The Lancet Rheumatology. 2026. DOI: 10.1016/S2665-9913(26)00107-4

URL: https://doi.org/10.1016/S2665-9913(26)00107-4

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