Tofacitinib treatment modulates the levels of several inflammation-related plasma proteins in rheumatoid arthritis and baseline levels of soluble biomarkers associate with the treatment response.

The data on effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analysed how tofacitinib treatment and thus inhibition of the Janus kinase - signal transducer and activation on transcription pathway affects the in vivo levels of inflammation-related plasma proteins in RA patients. In this study, sixteen patients with active RA [28-joint Disease Activity Score (DAS28) >3.2] despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) started tofacitinib treatment 5mg twice daily. Levels of 92 inflammation-related plasma proteins were determined by proximity extension assay at baseline and at three months. Tofacitinib treatment for three months, in csDMARD background, decreased mean DAS28 from 4.4 to 2.6 (p<0.001). Marked (>20%) and statistically significant (p<0.05) changes were found in the levels of 21 proteins, 18 of which decreased and three increased. Of these proteins 17 are directly involved in inflammatory responses or in the cellular response to cytokines. Highest (>50%) decrease was observed for interleukin-6 (IL-6), C-X-C motif chemokine ligand 1, matrix metalloproteinase-1 and AXIN1. Higher baseline level of IL-6, and lower levels of C-C motif chemokine 11 and Delta and Notch-like epidermal growth factor-related receptor were associated with DAS28 improvement. Our results indicate that tofacitinib downregulates several proinflammatory plasma proteins which may contribute to the clinical efficacy of tofacitinib. In addition, soluble biomarkers may predict the treatment response to tofacitinib.