Background/Purpose: Tocilizumab (TCZ) is an anti-IL6R monoclonal antibody approved for the treatment of Rheumatoid Arthritis (RA). There is limited data on synovial tissue histology changes. The aim of this study was to characterize the synovial tissue histological changes after treatment with TCZ and to investigate the effect of treatment on citrullination.

Methods: 15 patients with definite RA, according to ACR 1987 criteria, independent of disease duration, who failed treatment with at least one conventional synthetic or biologic disease modifying anti-rheumatic drug (DMARD) were included. Synovial biopsies were obtained before and after 8 weeks of treatmentwith TCZ from all patients. Clinical evaluation was performed at baseline and at the time of the second synovial biopsy. We evaluated by immunohistochemistry (IHC) expression of citrullinated proteins (CP) and protein arginine deiminase (PAD) enzymes in synovial tissue before and after treatment with TCZ (C03, B09, BVCA1, PAD2, PAD4). Negative controls were used for each antibody. Expression of CD68, CD3 and CD55 was also evaluated. Evaluation of all IHC variables was performed by two blinded independent observers using a semiquantitative score on a 0–3 scale (0, no staining; 1, low amounts of staining; 2, moderate amounts of staining; 3, high amounts of staining). Paired-wised Wilcoxon Signed Ranks Test was used to compare the median value before and after treatment.

Results:

The median (IQR) age, disease duration, N. prior biologic DMARDs and DAS28 at baseline was 66 (58-79), 4 (1-13), 1 (0-2), 6 (5-7), respectively. 93% were female, 53% were RF + and 60% ACPA+, 53% had concomitant glucocorticoids and only 27% had concomitant conventional synthetic DMARDs. Significant reductions in DAS28, swollen and tender joint count (SJC and TJC, respectively), and acute phase reactants (ESR and CRP) were observed between baseline and 8 weeks (table 1). By IHC, TCZ induced significant decrease in the number of CD3, C03 and CD55, but not in the number of the other CP, PAD2, PAD4 and CD68 (table 1). No significant correlations between reduction in disease activity (by ΔDAS28, ΔSJC, ΔTJC, ΔESR, ΔCRP) and reduction in CP, CD68 or CD3 were found.

Conclusion: IL6R blockade leads to significant decrease in synovial T-cell count. No clear impact on citrullination was observed. Interestingly, no effect on the number of macrophages was found.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/significant-decrease-of-t-cells-but-not-macrophages-in-the-synovium-of-patients-with-active-rheumatoid-arthritis-after-treatment-with-tocilizumab/