Background Etanercept (ETN) is effective anti-TNF treatment for rheumatoid arthritis (RA). Calprotectin (CP) and Matrix metalloproteinase-3 (MMP-3) are biomarkers associated with disease activity and joint destruction in RA. Ultrasonography (US) is a reliable method for detection and evaluation of synovitis.
Objectives To explore associations between CP, MMP-3 serum levels and US synovitis score (B-mode -BM and power Doppler-PD) in RA patients during ETN therapy.
Methods 26 subjects aging ≥18 years with moderate-to-severe RA despite stable doses of conventional DMARDs (DAS28 6,22±0,91) had received ETN 50 mg weekly subcutaneously for 24 weeks. The mean age was 50,8±13,5 years, mean RA duration 6,9±6,1 years, 88% were women, 65% were RF+. Routine clinical and laboratory evaluation was done at weeks 0 and 25. US examination was performed before start of ETN treatment and after 6 month of ETN therapy by the same independent sonographer. 7-joint score (grade 0-3) included wrist, intercarpal, 2-3 MCP, 2-3 PIP joints of the clinically dominant hand and knee was used. CP and MMP-3 serum levels (ELISA) were measured at the same time points. Associations between US sum scores, CP, MMP-3, CRP, ESR and DAS28 were evaluated.
Results All clinical, laboratory and US parameters of RA activity had significantly improved during ETN therapy (table 1)
We did not determine any associations between Me Δ CP and MMP-3 with Me Δ of US synovitis score (both BM and PD).
We explored the significant correlation between baseline CP, MMP-3 serum levels and BM sum score at week 25 (r=0,61 and 0,44 respectively) (Fig.1)
Despite achievement remission/low disease activity according EULAR subclinical synovitis was detected in the most patients (n=24, 92%) at week 25.
Conclusions US sum score decreased significantly in parallel with CP and MMP-3 serum levels during ETN therapy. There was not any correlation of MeΔ CP and MMP-3 with MeΔ US sum score. CP and MMP-3 baseline concentrations strongly correlated with B-mode score at week 25. High baseline CP and MMP-3 levels may be predictive factors of poor response to ETN treatment. Our findings support that CP and MMP-3 are useful biomarkers for monitoring of synovitis in RA during anti-TNF therapy. US response is delayed in comparison with clinical effect and decrease in CP and MMP-3 concentrations.
Hammer HB, Fagerhol MK, Wien TN, Kvien TK. The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab. Arthritis Res Ther. 2011;13(5):R178.
Disclosure of Interest None declared