gms | German Medical Science

Objectives: Biological disease- modifying anti-rheumatic drugs (DMARDs) have strongly improved the treatments options for patients with rheumatoid arthritis. The first approved and most frequent biological drugs to be used in RA patients are TNFalpha inhibitors that have been shown to be effective and save. However, up to 30 percent of RA patients develop resistance of therapy characterized by sustained synovitis. In this study, we studied the synovial cell populations in rheumatoid patients with different clinical disease activity treated with methotrexate (MTX) or TNFalpha blockade.

Methods: Synovial biopsies were obtained from different joints of patients with rheumatoid arthritis that had been treated with MTX (n=18) or a TNFalpha antibody (n=44) for at least 12 month. DAS28-CRP scores and clinical parameters including disease duration and history of treatment were assessed at time point of surgery. 15 patients had active arthritis (DAS28-CRP >2.6), while 45 patients were in clinical remission (DAS28-CRP < 2.6). Samples were cut and hematoxylin and eosin stained. CD68, CD3, CD20, CD31 and KI67 immunohistochemistry were performed. General synovitis score (GSS) was assessed for each slide and quantitative scoring were performed for immunostaining (CD3, CD15, CD20, CD68 and Ki67), in a blind manner. Local refractory synovitis was defined as patients with DAS28-CRP < 2.6, only one clinical affected joint and high grate synovitis in GSS. All patients with local refractory synovitis (n=16) received TNFalpha inhibitors. All patients gave written consent to this study prior to surgery.

Results and conclusion: General synovitis score were significantly correlated with DAS28-CRP score (r=0.65, p=<0.001). Similarly, clinical disease activity was also significantly correlated with scores for CD3 (r=0.62, p=<0.001), CD15 (r=0.43, p=<0.001), CD20 (r=0.61, p=<0.001), CD68 (r=0.54, p=<0.001) and Ki67 (r=0.63, p=<0.001), respectively. While no differences in the immunohistochemistry scores between patients generally resistant to MTX and TNFalpha therapy were observed, local refractory synovitis was associated with significantly lower CD3 and CD20 scores.

In summary, GSS and immunohistochemistry scores for CD68, CD3, CD20, CD31 and KI67 generally reflect the clinical disease activity in RA. However, local refractory synovitis in patients treated with TNFalpha blockade display a distinct immunohistological profile with low CD3 and CD20 and high CD68 and Ki67 expression. This could help to develop tissue driven therapies in the futures.