AB0112 THE PREDICTIVE VALUE OF SERUM SOLUBLE ICAM-1 AND CXCL13 IN THE THERAPEUTIC RESPONSE IN RHEUMATOID ARTHRITIS PATIENTS

Abstract

Background:Tumor Necrosis Factor-α (TNFα) inhibitors (TNFi) have greatly improved the prognosis of RA, but not all these patients respond well to TNFi. So far there has been no definite biomarker to predict the response to TNFi yet.Objectives:The aim of current study was to explore the predictive value of sICAM-1 and CXCL13 on the response to TNFα receptor fusion protein in RA patients who have poor response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).Methods:60 RA patients with disease duration more than 6 months and at least low disease activity definded by DAS28-CRP>3.2 although after csDMARDs treatment for more than 3 months were included. They were further treated with TNFα receptor Fc fusion protein and MTX 10mg per week for 12 weeks. Soluble ICAM-1 (sICAM-1) and CXCL13 concentrations in sera from 60 RA patients and 20 healthy controls were tested by ELISA right before and at the end of 12 weeks of TNFi therapy. The correlation between sICAM-1 and CXCL13 with disease activity and their predictive values for TNFi response were analyzed.Results:The mean age of the 60 patients were 54.8±11.6 years. Serum sICAM-1 and CXCL13 concentration was higher in RA patients than heathy controls, higher in seropositive RA patients than in seronegative ones, and higher in RA patients with higher disease activity (table 1). Serum sICAM-1 and CXCL13 levels were decreased after TNFi therapy, especially in good responders (table 2). Baseline sICAM-1 concentration was independently associated with EULAR response (p=0.033, OR=1.014, 95% CI=1.003-1.026). The sICAM-1high/CXCL13highpatients had the highest response rate, which was significantly higher than the sICAM-1low/CXCL13lowgroup (OR=8.143, 95%CI:1.040-75.482, p=0.045).Table 1.The correlation between serum sICAM-1 and CXCL13 concentrations and disease activity at baseline and 12 weeks after treatment.BaselinesICAM-1 (ng/mL) CXCL13 (pg/mL)Week 12sICAM-1 (ng/mL) CXCL13 (pg/mL)rprprprpDAS28-ESR0.3960.0020.2330.0730.3150.0140.1500.254DAS28-CRP0.3600.0050.1910.1430.2500.0540.0620.639SDAI0.2780.0320.1380.2920.2200.0910.0420.750CDAI0.2770.0320.1160.3770.1820.1630.0090.943Table 2.The comparisons of sICAM-1 and CXCL13 concentrations at baseline and 12 weeks based on different response criteria.EULAR responder EULAR non-responderACR 20 achieved ACR 20 not achievedBaselineWeek 12pBaselineWeek 12pBaselineWeek 12pBaselineWeek 12psICAM-1 (ng/ml)(mean±SD)388.5±94.0325.3±83.70.001302.1±56.1334.3±61.50.270390.5±95.8329.6±87.60.004345.7±85.3329.3±67.90.513CXCL13 (pg/ml)(median, min-max)190.6(50.1-2081.4)103.3(4.8-1497.8)0.003120.4(18.8-1909.4)144.7(18.4-2155.0)0.546199.7(57.9-2081.4)103.8(8.9-2155.0)0.011136.0(18.8-1909.4)102.2(4.8-767.33)0.531Conclusion:sICAM-1 and CXCL13 are elevated in RA patients and correlated with disease activity. sICAM-1 is an independent predictor of TNFi response in csDMARDs refractory RA patients.