Temporal evolution of synovial histopathology in rheumatoid arthritis across treatment periods: a large-scale analysis of 1770 surgical specimens using the Rooney score.

چکیده اصلی

OBJECTIVES: To evaluate temporal changes in rheumatoid arthritis (RA) synovial histopathology across treatment periods using the Rooney score in a surgical cohort. METHODS: This retrospective study included 1770 synovial specimens from 1150 patients who underwent orthopaedic surgery between 2011 and 2025. Specimens were classified into early biological disease-modifying antirheumatic drug (bDMARD) (2011-2013), established bDMARD (2014-2018) and contemporary targeted therapy (2019-2025) periods. Mixed-effects models included patient-level random intercepts. Sensitivity analyses used calendar year, 3-year intervals, specimen-count-based tertiles and operated-joint power Doppler (PD) grade. RESULTS: The median total Rooney scores were 29 (IQR 20-36), 24 (19.25-34) and 23 (20-32) across the periods (p for trend <0.001), driven by lower lymphocytic infiltration. The combined lymphocytic infiltration score decreased from 11 (0-20; early period) to 2 (0-11; contemporary period). After full adjustment, the contemporary period remained associated with a lower Rooney score than the early period (β -1.61, 95% CI -2.74 to -0.48; p=0.005). Tertile analyses were consistent, whereas adding operated-joint PD grade attenuated period estimates. Janus kinase (JAK) inhibitor-treated specimens did not have lower scores than bDMARD-treated specimens without JAK inhibitor exposure. Residual lymphocytic infiltration remained detectable despite clinical or imaging remission. CONCLUSIONS: RA synovial histopathology evolved across treatment periods, with lower Rooney scores and marked reductions in lymphocytic infiltration. These changes appear to reflect broader contemporary RA management rather than a JAK inhibitor-specific effect, although tissue-level inflammation may persist despite clinical or imaging remission.

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