Going Further: Comprehensive Disease Control of Rheumatoid Arthritis, Targeting Cytokines and Chemokines

OBJECTIVES: Mechanism of action of biological and synthetic disease-modifying antirheumatic drugs (DMARDs) includes the inhibition of specific proinflammatory cytokines. This study aimed to elucidate the cytokines and chemokines inhibited by different treatments (conventional synthetic DMARD [csDMARD], biological and targeted synthetic DMARD) in rheumatoid arthritis (RA). METHODS: Fifty-nine RA patients with low disease activity or remission included in a cross-sectional study were classified by treatment in groups: abatacept, certolizumab, rituximab (RTX), tocilizumab, tofacitinib (TOF), baricitinib (BAR), and csDMARD. Cytokine and chemokine serum levels were measured by LEGENDplex Human Inflammation panel. Quantitative variables were compared using Student t or Mann-Whitney U test as appropriate, whereas qualitative variables were compared using χ(2) or Fisher exact test. p < 0.05 was considered significant. RESULTS: Certolizumab, RTX, tocilizumab, and TOF showed that most cytokine pathways inhibited: tumor necrosis factor α, interferon γ, interleukin 1β (IL-1β), IL-12, IL-18, and IL-23; in addition, csDMARDs showed a similar inhibition patron except for IL-23. Serum level of tumor necrosis factor α pathway was one of the most inhibited being undetectable in RTX, TOF, and BAR groups. Interleukin 6 was shown to be inhibited by abatacept, RTX, and TOF; however, higher levels were observed in 3 patients treated with tocilizumab. Abatacept, certolizumab, RTX, and TOF downregulated IL-10 in this group of patients but remained detectable in almost half of the subjects, with the highest levels in the BAR group. The active pathways that remained the most were CC chemokine ligand 2, IL-8, IL-17, and IL-33. CONCLUSIONS: Understanding the cytokine chemokine pathways inhibition could help rheumatologists to prescribe a tailored therapy using the arsenal of DMARDs for individualized RA treatment in an evidence-based decision manner.