Abstract
Introduction. Nonsteroidal anti-inflammatory drugs and methotrexate frequently treat autoimmune diseases such as rheumatoid arthritis (RA), ulcerative colitis, psoriasis, and ankylosing spondylitis.
Methotrexate regimen can be combined with parenteral biological therapy, which has become very effective. There are four proteins in the Janus kinase (JAK) family are involved in the pathogenesis of autoimmune diseases, together with seven transcription factors for signal transductors and activators of transcription (STATs). STATs mediate intracellular signal transduction from cytokine receptors directly to the nucleus. Targeting the JAK signaling pathway has shown promising results in the treatment of many autoimmune diseases. Specifically, JAK inhibitors, also known as jakinibs are drugs that inhibit the activity of one or more enzymes of the JAK family (JAK1, JAK2, JAK3, TYK2), thereby blocking the JAK-STAT signaling pathway.
Objective. The aim of the review is to draw attention to the mechanism of action of JAK inhibitors and their safety profile.
Discussion. JAK inhibitors are often incorrectly classified as biological drugs. The effectiveness of JAK inhibitors was proven in several clinical trials, but there have been concerns raised regarding their safety.
Conclusion. In February 2022, the EMA Safety Committee began investigating the safety of JAK inhibitors for suspected risk of cardiovascular adverse effects, frequent infections, and thromboembolic events. Despite many studies, there is still no definite attitude and JAK inhibitors remain promising drugs for the autoimmune system (Tab. 2, Fig. 2, Ref. 23). Text in PDF www.lekarskyobzor.sk.
KEY WORDS: autoimmune diseases, Janus kinase inhibitors, rheumatoid arthritis.
Lek Obz 2022, 71 (11): 512-517
Andrey ŠVEC 1, Simona VALÁŠKOVÁ 2, Andrea GAŽOVÁ 3, Ján KYSELOVIČ 4,5
1 1. ortopedicko-traumatologická klinika, Lekárska fakulta Univerzity Komenského, Bratislava
2 Centrum vedecko-technických informácií, Bratislava, vedúci prof. PharmDr. J. Kyselovič, CSc.
3 Ústav farmakológie a klinickej farmakológie, Lekárska fakulta Univerzity Komenského, Bratislava, prednosta
prof. MUDr. M. Wawruch, PhD.
4 V. interná klinika Lekárskej fakulty Univerzity Komenského v Bratislave, prednosta prof. MUDr. J. Payer, PhD., MPH, FESC
5 Katedra farmakológie a toxikológie, Univerzita veterinárneho lekárstva a farmácie v Košiciach, prednosta prof. MVDr. J. Legáth, CSc.
CITE
ŠVEC A., VALÁŠKOVÁ S., GAŽOVÁ A. et al.: The mode of action of the inhibitors JAK kinasis and their using in the clinical praxis. Lek Obz 2022, 71 (11): 512-517
