Effects of methotrexate and tofacitinib on gene expression of activated rheumatoid arthritis fibroblast-like synoviocytes

Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators. Overall design: Primary RA-FLS (n = 3 biological replicates) were pre-treated with MTX or TOFA for 24 h, then activated by stimulation with interleukin-1b and platelet-derived growth factor in the presence or absence of MTX or TOFA for 48 h prior to RNA-seq.