Etanercept decreases synovial expression of tumour necrosis factor-α and lymphotoxin-α in rheumatoid arthritis

Abstract

Objectives: Etanercept is an effective tumour necrosis factor (TNF)-α inhibitor drug with the unique ability to block not only TNF-α but also lymphotoxin (LT)-α, at least in vitro. We aimed to investigate the in vivo effect of etanercept on synovial expression of TNF-α and LT-α.

Method: Synovial biopsies from 12 rheumatoid arthritis (RA) patients started on etanercept and 11 RA patients started on infliximab were obtained at baseline and 8 weeks after treatment initiation. Synovial expression of TNF-α and LT-α was evaluated by immunohistochemistry followed by computer-assisted image analysis. Differences between paired samples were analysed by the Wilcoxon test and between groups by the Mann–Whitney test. A p-value < 0.05 was considered statistically significant.

Results: Six out of the 12 of the patients started on etanercept achieved an American College of Rheumatology (ACR)50 response. Macroscopic evaluation of the joints during arthroscopy revealed a significant decrease of local inflammation mainly in good ACR50 responders. Synovial expression of both LT-α and TNF-α decreased but the differences did not reach statistical significance at a group level. By contrast, a significant decrease in both LT-α and TNF-α was observed when only good ACR50 responders were analysed. Despite higher levels of baseline synovial TNF-α in the good responders, neither baseline LT-α nor TNF-α could predict clinical response after 8 weeks. A decreasing trend of the synovial levels of LT-α was also observed in good responders to infliximab, but the difference did not reach statistical significance.

Conclusions: Etanercept treatment modulates the synovial expression of both TNF-α and LT-α in vivo, a mechanism that might partly explain its clinical efficacy in RA.

Acknowledgements

This research has received funding from the Initial Training Networks 7th Framework Programme Osteoimmune (289150), the European 7th Framework Programme (FP7/2007-2013) Euro-TEAM (305549), the Innovative Medicines Initiative ‘Be The Cure’ (115142-2), and the Swedish Research Council.