AB0112 THE PREDICTIVE VALUE OF SERUM SOLUBLE ICAM-1 AND CXCL13 IN THE THERAPEUTIC RESPONSE IN RHEUMATOID ARTHRITIS PATIENTS
Authors: J. Zhao, X. Ye, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

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&gt;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-1 high /CXCL13 high patients had the highest response rate, which was significantly higher than the sICAM-1 low /CXCL13 low group (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. Baseline sICAM-1 (ng/mL) CXCL13 (pg/mL ) Week 12 sICAM-1 (ng/mL) CXCL13 (pg/mL ) r p r p r p r p DAS28-ESR 0.396 0.002 0.233 0.073 0.315 0.014 0.150 0.254 DAS28-CRP 0.360 0.005 0.191 0.143 0.250 0.054 0.062 0.639 SDAI 0.278 0.032 0.138 0.292 0.220 0.091 0.042 0.750 CDAI 0.277 0.032 0.116 0.377 0.182 0.163 0.009 0.943 Table 2. The comparisons of sICAM-1 and CXCL13 concentrations at baseline and 12 weeks based on different response criteria. EULAR responder EULAR non-responder ACR 20 achieved ACR 20 not achieved Baseline Week 12 p Baseline Week 12 p Baseline Week 12 p Baseline Week 12 p sICAM-1 (ng/ml) (mean±SD) 388.5±94.0 325.3±83.7 0.001 302.1±56.1 334.3±61.5 0.270 390.5±95.8 329.6±87.6 0.004 345.7±85.3 329.3±67.9 0.513 CXCL13 (pg/ml) (median, min-max) 190.6 (50.1-2081.4) 103.3 (4.8-1497.8) 0.003 120.4 (18.8-1909.4) 144.7 (18.4-2155.0) 0.546 199.7 (57.9-2081.4) 103.8 (8.9-2155.0) 0.011 136.0 (18.8-1909.4) 102.2 (4.8-767.33) 0.531 Conclusion: 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. References: [1]Han BK, Kuzin I, Gaughan JP, et al. Baseline CXCL10 and CXCL13 levels are predictive biomarkers for tumor necrosis factor inhibitor therapy in patients with moderate to severe rheumatoid arthritis: a pilot, prospective study. Arthritis Res Ther, 2016, 18: 93. [2]Greisen SR, Schelde KK, Rasmussen TK,et al. CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’. Arthritis Res Ther, 2014, 16(5): 434. [3]Klimatcheva E, Pandina T, Reilly C, et al. CXCL13 antibody for the treatment of autoimmune disorders. BMC Immunol, 2015, 16: 6. Disclosure of Interests: None declared