INTESTINE Vol.25 No.3(6)

Theme An up-to-date review of the molecular-targeted therapies for inflammatory bowel disease
Title Janus kinase inhibitors
Publish Date 2021/09
Author Toshiyuki Sakurai Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine
Author Masayuki Saruta Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine
[ Summary ] A large number of cytokines, which bind to receptors on the cell surface and transmit stimuli into the nucleus via the intracellular Janus Kinase (JAK) signal transducer and activator of transcription pathway are involved in the pathophysiology of inflammatory bowel disease. There are four subtypes of the cytokine receptor intracellular tyrosine kinase JAK. such as JAK1, JAK2, JAK3, and TYK2, and the cytokine-induced action differs based on the combination of these subtypes. Tofacitinib, a JAK inhibitor produces a strong immunosuppressive effect through specific suppression of JAK1 and JAK3, which are important cytokine-related inflammatory pathways. International clinical trials including those 284 INTESTINE volume 25, number 3, 2021. performed in Japan (OCTAVE 1, OCTAVE 2, and OCTAVE Sustain) have confirmed the efficacy of tofacitinib for the treatment of moderate-to-severe active ulcerative colitis. However, JAK inhibitor therapy is reportedly associated with a high risk of infections such as herpes zoster, as well as coronary artery disease and thromboembolism.
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