gms | German Medical Science

Objectives: The purpose of this study was to investigate the relationship between clinical disease activity in patients with advanced stage rheumatoid arthritis (RA) on treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and histopathological scores of synovial inflammation.

Methods: This study included 62 consecutive patients with rheumatoid arthritis that underwent surgery for either isolated synovectomy (n=30 patients) or total joint replacement plus synovectomy or arthrodesis (n=32). Diagnosis of RA was made according to the ACR criteria. Inclusion criterea were ongoing medication prior to surgery for at least six months with either methotrexate or a TNFalpha inhibitor. Patients with different DMARD medication were excluded. Disease activity was evaluated using DAS28-CRP score (four variables, CRP-based), CDAI and SDAI at the time point of surgery. Synovial biopsies were taken intraoperatively, fixed overnight in formalin buffer and embedded in paraffin for histologic and immunohistochemical analyses. Serial histologic sections were stained with hematoxylin and eosin. Immunostaining for CD3, CD15, CD20 and CD68 were performed on an automated staining system.

Results and conclusion: The clinical disease activity index (CDAI) was significantly correlated with both the GSS and the IMSYC (r=0.65, p=<0.001, r=0.67, p=<0.001). Compared to patients with moderate and high disease activity, there was a significantly lower expression of T cell (CD3), B cell (CD20) and neutrophil (CD15) markers in synovial tissue of patients with low activity, but similar expression of the macrophage marker CD68. Subgroup analyses revealed no differences between small and large joints, seropositive and seronegative RA and patients with or without prednisolone treatment. However, we found a significantly stronger correlation of CDAI with IMSYC in patients undergoing arthroplasty (r=0.82) than in patients undergoing synovectomy (r=0.55). In addition, there was a stronger correlation of CDAI with GSS in patients treated with methotrexate (r=0.86) than in patients with TNFalpha blockade (r=0.55). In conclusion, the study demonstrates that the histopathological scores GSS and IMSYC in general reflect clinical disease activity in patients with advanced stage rheumatoid arthritis, but that there is some heterogeneity between subgroups of patients within the cohort. In the future, molecular characterization of synovial inflammatory cell populations will help to further defined clinically important subtypes of RA.