The predictive value of serum soluble ICAM-1 and CXCL13 in the therapeutic response to TNF inhibitor in rheumatoid arthritis patients who are refractory to csDMARDs

Abstract

Background: Tumor necrosis factor-α (TNFα) inhibitors (TNFi) have greatly improved the prognosis of RA and become the first therapeutic option for patients who failed the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) therapy, but not all these patients respond well to TNFi. So far, there has been no definite biomarker to predict the response to TNFi yet.

Methods: Sixty rheumatoid arthritis (RA) patients with disease duration more than 6 months and at least low disease activity defined by DAS28-CRP > 3.2 although after csDMARDs (including MTX and/or leflunomide) treatment for more than 3 months were included. They were further treated with TNFα receptor Fc fusion protein and MTX 10 mg 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 was 54.8 ± 11.6 years. Serum sICAM-1 and CXCL13 concentrations were 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. Serum sICAM-1 and CXCL13 levels were decreased after TNFi therapy, especially in good responders. Baseline sICAM-1 concentration was independently associated with the 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).

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. Key Points • This study confirmed the predictive value of soluble ICAM-1 (sICAM-1) and CXCL13 on the response to TNFi in RA patient. • Baseline sICAM-1 concentration was independently associated with the EULAR response. • The sICAM-1^high/CXCL13^high patients had significantly higher response rate than the sICAM-1^low/CXCL13^low group.

Keywords: CXCL13; Predictive biomarker; Response; Rheumatoid arthritis; TNF inhibitor; sICAM-1.