Background Tocilizumab is an approved humanized anti-IL-6 Receptor antibody with proven therapeutic benefits in the treatment of patients with RA.
Objectives This study aimed to investigate the global molecular effects of Tocilizumab versus Methotrexate therapy in synovial biopsy samples obtained from early RA patients harvested prospectively before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients.
Methods Paired synovial biopsy samples were obtained from the affected knee of early RA patients before and 12 weeks after initiation of Tocilizumab (n=12) or Methotrexate (n=8) therapy. Total RNA was extracted, labeled according to standard Affymetrix procedures, and hybridized on GeneChip HGU133 Plus 2.0 slides. Quantitative real-time reverse transcriptase-polymerase chain reaction (qPCR) experiments were performed to confirm the differential expression of selected transcripts.
Results We found that Tocilizumab induces a significant down-regulation of genes included in specific pathways: cytokines (IL-6, IL-7, IL-22, ...) & chemokines (CCL8, CCL11, CCL13, CCL19, CCL20, CXCL5, CXCL13, ...), and T cell activation. By contrast, Tocilizumab induces a significant up-regulation of genes associated with healing processes. These effects are significantly more pronounced as compared with the effects of Methotrexate, Rituximab, and Adalimumab therapies.
Real-time qPCR experiments, performed until now, confirm the down-regulation of CXCL13 and up-regulation of BMPR1A expression following Tocilizumab treatment.
Conclusions Tocilizumab displays distinct molecular effects on synovial biopsies of RA patients. These results open perspectives for the individualization of therapeutic decisions, based on the molecular profiles of the patients.
Disclosure of Interest None Declared