Abstract
IntroductionThe need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual’s mediator production in explants obtained at baseline.MethodsRA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman’s rank correlations were performed. P-values below 0.05 were considered statistically significant.Results16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.ConclusionsSynovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.
Highlights
The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident
interleukin 6 (IL-6) production in biologic disease modifying anti-rheumatic drug treatment (bDMARD)-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high disease activity score 28 joints C-reactive protein (DAS-28) (ρ = 0.57, P = 0.03), colour Doppler ultrasound (CDUS) (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up
We recently demonstrated that synovial explants produce IL-6, monocyte chemo-attractant protein 1 (MCP-1) and macrophage inflammatory protein 1 beta (MIP-1b), and that this production was associated with colour Doppler ultrasound (CDUS) activity, magnetic resonance imaging (MRI) findings of synovitis, bone marrow oedema (BME), and erosions, using the RA MRI score (RAMRIS) and disease activity score 28 joints C-reactive protein (DAS-28) [16]
Summary
The aim of this study was to explore whether in vitro effects of a bDMARD on the individual’s baseline RA synovial explants were associated with the in vivo treatment response to the same bDMARD, both clinically and by imaging
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