Background Calprotectin (CP) is potentially more sensitive biomarker of disease activity in rheumatoid arthritis (RA) than conventional acute-phase reactants because it directly reflects inflammation in the synovium rather than systemic inflammation.
Objectives to evaluate relationship between serum CP levels, disease activity, matrix metalloproteinase-3 (MMP-3) concentration and response to Etanercept (ETN) therapy in RA patients.
Methods 84 patients with moderate-to-severe RA despite stable doses of cDMARDs received ETN 50 mg weekly for 24 weeks. The mean age was 52±13,3 years; 85% (n=71) were females; the median disease duration was 9,3±8,3 years; RF+ and ACCP + were 81% (n=68) and 83% (n=70), extraarticular manifestations were found in 18% (n=15); 62% (n=52) used MTX, 26% (n=22)-LEF, 11% (n=9)-other DMARDs, 38% (n=32) -corticosteroids ≤10 mg/day. 60% (n=50) had used another biologics prior to start of ETN. Baseline disease characteristics (Me [Q25–75]): patient disease activity, VAS, mm: 63 [49-75]; TJC: 12 [9-16]; SJC: 9 [7-12]; CRP, mg/l: 23,7 [8,25-46,8]; ESR, mm/h: 46 [29-67]; RF, IU/ml: 122,5 [17,45-313,15]; ACCP, U/ml: 181,2 [43,6-300]; DAS28 6,35 [5,72-6,81]; CP, μg/ml 5,34 [2,12-10,98]; MMP-3, ng/ml 1,01 [0,64-1,67].Response was defined as achievement of good/moderate response according EULAR at weeks 12, 25. Serum CP and MMP-3 levels were evaluated with ELISA at weeks 0, 12, 25. Serum samples from 21 healthy subjects served as control.
Results There wasn't significant difference in median CP level between patients with RA compared to healthy controls (5,34 vs 4,17, p=0,26) at baseline, possibly due to small size of control group. Highly significant correlations were found in RA patients between CP baseline level and ESR, CRP, MMP-3 and DAS28 at week 0: CRP (r=0,69,p<0,0001), ESR (r=0,41,p<0,0001), MMP-3 (r=0,47,p<0,0001), DAS28 (r=0,37,p<0,0001). The similar data were determined at weeks 12 and 25. We didn't find strong correlations between CP level and clinical parameters of disease activity. CP serum level decreased after 6 months of ETN treatment (p<0,0001). ROC analysis provided an AUCroc of 0.8±0,06 (95%CI 0,68-0,91) for the differentiation of RA patients and healthy control. A cut-off value of 0,67 μg/ml resulted in sensitivity and specifity values of 73 and 86% respectively.There wasn't found predictive value for CP baseline level and good/moderate EULAR response to ETN treatment (AUCroc=0,41±0,07; p=0,18; 95%CI 0,28-0,54).
Conclusions CP level strongly correlates with laboratory parameters of joint inflammation and bone destruction (MMP-3) and significantly decreases in response to ETN treatment. There was not prognostic association between CP baseline level and response to ETN treatment. This result indicate that CP is a promising marker for assessment and monitoring of disease activity in RA patients. CP prognostic value is unclear, futher investigations are required to evaluate it.
Disclosure of Interest None declared
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