CXCL10 and CXCL13 baseline levels: predictive biomarkers for TNF inhibitor therapy in rheumatoid arthritis patients
Rheumatoid arthritis (RA) is characterized by synovial inflammation, cartilage and bone destruction and systemic features. Tumor necrosis factor (TNF) inhibitors are used to treat moderate to severe RA patients who have inadequate responses to conventional disease-modifying anti-rheumatic drugs including methotrexate.
However, reliable predictive biomarkers of therapeutic response for TNF inhibitor therapy are lacking. To overcome this problem, a study was conducted to investigate that chemokines may present useful biomarkers to predict the response to TNF inhibitor therapy in rheumatoid arthritis.
In the conducted trial, RA patients who were initiating adalimumab or etanercept were recruited from the rheumatology clinics at Cooper University Hospital. They were evaluated at baseline and 14 weeks after TNF inhibitor therapy and serum levels of CXCL 10, CXCL13 and CCL20 were measured by ELISA. Responders (n=16) were defined as patients who had good or moderate response at week 14 by EULAR response criteria and nonresponders (n=13) were defined as having no response.
Results indicated that the responders had higher levels of baseline CXCL 10 and CXCL 13 compared to nonresponders (p= 0.03 and 0.002 respectively). There was no difference in CCL20 levels. CXCL 10 and CXCL 13 were highly correlated with each other and were higher in seropositive RA patients. CXCL 10 and CXCL 13 levels were decreased after TNF inhibitor therapy in responders. Baseline additive levels of CXCL 10 + 13 were correlated with changes in DAS score at 14 weeks after TNF inhibitor therapy and ROC curve analyses for predictive ability of CXCL 10 + 13 showed an AUC of 0.83.
At last, it was concluded that elevated baseline levels of CXCL 10 and CXCL 13 were associated with favorable response to TNF inhibitor therapy in RA. However, subjects with high CXCL 10 and high CXCL 13 may represented a subset of RA patients whose inflammatory reactions are primarily driven by tumor necrosis factor.