Abstract
The relationship between the systemic immune-inflammation index (SII) and disease activity in rheumatoid arthritis (RA) remains unclear. This study aimed to clarify this association in a cohort of hospitalized RA patients overwhelmingly with moderate-to-high disease activity. We consecutively included 1,191 RA patients hospitalized at Xingtai People's Hospital from March 2022 to December 2024. SII was calculated as (neutrophils × platelets)/lymphocytes. Disease activity was assessed using the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28ESR) and C-reactive protein (DAS28-CRP). Multiple linear regression and generalized additive models were employed to explore the association between SII and disease activity. For regression analysis, SII underwent natural logarithm transformation to improve normality. After strict eligibility criteria, 997 individuals (mean age 57.66 years; 77.93% female, 95.6% moderate-to-high disease activity) were included for the final analysis. A nonlinear relationship was identified with a threshold at LnSII = 5.56 (SII = 260.36). Above this cutoff, LnSII showed positive correlations with both DAS28-ESR (β = 0.53, 95% CI: 0.44-0.63) and DAS28-CRP (β = 0.63, 95% CI: 0.53-0.72). No significant association was found below this threshold (DAS28-ESR: β = -0.56, 95% CI: -1.13- 0.02; DAS28-CRP: β = -0.35, 95% CI: -0.91-0.20). These findings suggest SII levels were independently positive associated with DAS28-ESR and DAS28-CRP among RA patients with SII > 260.36, supporting its potential as a useful biomarker for evaluating disease activity in RA patients with predominantly moderate-to-high disease activity.