Low baseline interleukin-17A levels are associated with better treatment response at 12 weeks to tocilizumab therapy in patients with rheumatoid arthritis

Abstract

Background: A significant subset of patients with rheumatoid arthritis (RA) does not respond to tocilizumab (TCZ). However, the factors associated with treatment failure have not been well defined. The study was aimed to identify novel biomarkers which might help predict treatment response to TCZ in RA patients who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs). Methods: This study was designed as an independent sub-study of the CWP-TCZ301 , a 24-week, randomized, double–blinded trial of TCZ in RA patients with an inadequate response to DMARDs. Serum levels of cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-17A, IL-21 and IL-23 were determined by luminex multiplex analysis. IL-6 and soluble IL-6 receptor (sIL-6R) were measured by enzyme linked immunosorbent assay (ELISA). Results: Baseline IL-17A levels were significantly lower in patients who achieved the remission at 12 weeks of TCZ treatment as compared to patients who did not (mean ± SEM, 3.50 ± 2.94 vs 7.34 ± 3.34 pg/ml, p = 0.036). Patients were stratified into IL-17A low group and IL-17A high group as baseline levels. Significantly higher proportion of the patients with IL-17A low group achieved disease activity score 28 (DAS28) remission as compared to those with IL-17A high group (47.6 vs 17.4%, p = 0.032). Further, DAS28 improvement was significantly better in the former group than in the latter group at 12 weeks (3.15 ± 0.21 vs 2.66 ± 0.17, p = 0.045) and 24 weeks (3.47 ± 0.23 vs 2.99 ± 0.22, p = 0.046). Conclusion: Low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.