JAK Inhibitors in Rheumatology

In Germany, baricitinib and tofacitinib have been approved for the treatment of at least moderately active rheumatoid arthritis after the failure of conventional disease modifying anti-rheumatic drugs in 2017, and tofacitinib also for psoriatic arthritis and ulcerative colitis. Both baricitinib and tofacitinib can be taken orally and reversibly inhibit Janus kinases (JAK) and therefore the signaling of a large number of cytokines via the JAK/STAT pathway. JAK inhibitors have been shown to be at least as efficacious in rheumatoid arthritis as adalimumab and tofacitinib was also efficacious in psoriatic arthritis. Since they inhibit many cytokines, it is likely that in the future they will be applied for the treatment of further chronic inflammatory disorder such as connective tissue diseases and vasculitis. The adverse events of JAK inhibitors are comparable to those observed with biologicals, only herpes zoster is slightly more common. In the placebo-controlled trials, venous thromboembolic events (VTE) were more common in the baricitinib treated patients. The VTE rate does not appear to be elevated in baricitinib treated patients compared to RA cohorts however. In conclusion, JAK inhibitors are a powerful new treatment of RA and likely many other rheumatic diseases and fulfill an unmet need since they may be taken orally.