Synovial tissue macrophages: highly sensitive biomarkers for response to treatment in rheumatoid arthritis patients

Objective. Previous work identified synovial sublining macrophage numbers as a potential biomarker for clinical efficacy in rheumatoid arthritis (RA). Therefore, we investigated the association between changes in synovial macrophages infiltration and clinical improvement after antirheumatic treatment. Methods. 88 patients who participated in various clinical trials were studied. All patients underwent serial arthroscopy before initiation of treatment and after different time intervals. Immunohistochemical and digital image analysis was performed according to standardized procedures to detect changes in CD68+ synovial sublining macrophages in relationship to changes in the Disease Activity Score (DAS28). Statistical analysis was performed using oneway ANOVA, the independent samples t-test, linear regression, and the standardized response mean (SRM). Results. For the different groups according to the DAS28 response criteria (good, moderate, and non-responders) there was a statistically significant difference in the change in sublining macrophages (mean cells/mm ± SEM: -643 ± 124, -270 ± 64, and -95 ± 60, respectively; P<0.0003). There was a significant correlation between the change in the number of macrophages and the change in DAS28 (Pearson correlation 0.874, P < 0.01). The change in sublining macrophages could explain 76% of the variation in the change in DAS28 (P < 0.02). The sensitivity to change of the biomarker was high in actively treated patients (SRM > 0.8) while the ability to detect changes in placebo treated patients was weak (SRM <0.3). Conclusion. The results suggest that changes in synovial sublining macrophages can be used to predict possible efficacy of antirheumatic treatment.