Abstract
Janus kinase (JAK) inhibitors are synthetic small-molecule drugs which inhibit intracellular activity of several cytokines involved in the development of rheumatoid arthritis and other inflammatory rheumatic diseases. For the treatment of rheumatoid arthritis, tofacitinib, baricitinib and upadacitinib have already been approved.
Tofacitinib inhibits preferentially JAK1, JAK3 and to a lesser extend also JAK2, baricitinib inhibits JAK1 and JAK2 and upadacitinib is a selective JAK1 inhibitor. The efficacy of JAK inhibitors in clinical trials was significantly greater than placebo, greater than that of methotrexate, and at least comparable to that of biologic therapy.
Clinical efficacy of baricitinib and upadacitinib even outweighed the efficacy of adalimumab. Another indisputable advantage of JAK inhibitors is the possibility of oral administration.
As with other immunosuppressive drugs, long-term treatment with JAK inhibitors may be associated with more frequent infections, but their spectrum is different. Treatment with JAK inhibitors significantly increases the risk of herpetic infections, including herpes zoster, whilst reactivation of latent tuberculosis does not occur.
A specific, newly discussed problem of JAK inhibitor therapy is the higher incidence of thromboembolic events. JAK inhibitors are currently indicated for the treatment of moderate to severe rheumatoid arthritis, according to the EULAR guidelines in patients with RA and an insufficient therapeutic response to methotrexate.
The range of registered JAK inhibitors can be expected to further expand in the coming years.