Nonetheless, ex vivo studies in treated RA patients have shown that the inhibition of JAK-STATs is partial and reversible, which explains to some extent, the lack of severe, generalized drug-induced immuno-suppression.38 Notably, in spite of the (partially) distinct pharmacodynamic effects of the two compounds (ie, tofacitinib predominantly inhibiting JAK1/JAK3, baricitinib predominantly inhibiting JAK1/JAK2), their safety profile is very similar, suggesting that the actual in vivo effects might not be predicted entirely by in vitro “selectivity” assays. This evidence concerns the gene JAK1 and rheumatoid arthritis.