Multiplex analysis of laboratory biomarkers in assessing effectiveness of tocilizumab in treatment of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis (synovitis) and that can involve other tissues and organs. The use of biologics in clinical practice, including humanized monoclonal antibodies (IgG1) to interieukin-6 (IL-6R) receptors, it's the cause to search for predictors of response to this therapy. The aim of this study was to determine the relevance of multiplex cytokine analysis in evaluating the effectiveness of tocilizumab (TCZ) in RA. Materials and methods . We examined serum samples from 43 patients with RA. The comparison group was 297 healthy subjects matched by gender and age. Serum concentration of IgM and IgA rheumatoid factors (RF) and C-reactive protein (CRP) in serum was measured by immunonephelometry; of antibodies to cyclic citrullinated peptide (anti-CCP), antibodies to modified citrullinatedvimentin (anti-MCV), matrix metalloprotinase-3 (MMP-3) - by enzyme-linked immunosorbent assay; of cytokines - by xMAP technology. Results. At week 4 on TCZ therapy, patients with RA had a decrease serum levels of CRP, IgM RF, AMCV, MMP-3; on 8th - ESR, CRP, IgM and IgA RF, anti-CCP and anti-MCV, on the 24th - of all biomarkers, excluding anti-CCP. At 4th, 8th, 24th weeks of therapy, there was a decrease in serum levels of all studied cytokines (excluding IL-6 at 4th week and IL- 1ra at 8th and 24th weeks). The most associated factors witch effectiveness of TCZ are: MMP-3 (AUC0.7), anti-CCP (0.7) and VEGF (0.7). A predictive model based on the assessment of serum levels of this biomarkers can predicting the clinical response to TCZ in RA (AUC = 0.85; CI: 0.7-1.0). Conclusion. The data about association of basal serum concentrations of anti-CCP, MMP-3 and VEGF with the response in RA patients, made it possible to create a multiparameter index for predicting the TCZ effectiveness.