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JAK Inhibitors: Prospects in Connective Tissue Diseases

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Abstract

The dysregulation of the JAK–STAT pathway is associated with various immune disorders. Four JAK inhibitors have been approved for rheumatoid arthritis (RA), and numerous JAK inhibitors are currently being tested in phase II and III trials for the treatment of various autoimmune inflammatory diseases. In this narrative review, we elucidate the involvement of the JAK–STAT signaling pathway in the pathogenesis of connective tissue diseases (CTDs). We also discuss the efficacy of the first- and second-generation JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib, filgotinib, upadacitinib, solcitinib, itacitinib, decernotinib, R333, and pf-06651600) for CTDs including RA, systemic lupus erythematosus, dermatomyositis, systemic sclerosis, Sjögren’s syndrome, and vasculitis, based on laboratory and clinical research findings. JAK inhibitors have great potential for the treatment of various CTDs by reducing multiple cytokine production and suppressing inflammation, with the advantages of rapid onset in an oral formulation and decreased corticosteroid dependence and the associated adverse events, especially in refractory cases. We also highlight the safety of novel JAK inhibitors, which can cause opportunistic infections, especially viral infections. Being a very recent therapeutic option, information regarding the safety of JAK inhibitors during pregnancy and for pediatric use is limited. However, it is recommended that JAK inhibitors should be avoided in pregnant and breastfeeding women. More clinical data, especially on highly selective inhibitors, are required to judge the efficacy and safety of JAK inhibition in CTDs.

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Funding

This work was supported by the Chinese National Key Research R&D Program (grant number 2017YFC0907600, 2008BAI59B02, Chinese National High Technology Research and Development Program, Ministry of Science and Technology (grant number 2012AA02A513), CAMS Innovation Fund for Medical Sciences (grant number CIFMS2019-I2M-2-008) and the Fundamental Research Funds for CAMS&PUMC (grant number 2019PT330004).

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  1. Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuaifuyuan, Beijing, 100730, China

    Hanxiao You, Dong Xu, Jiuliang Zhao, Jing Li, Qian Wang, Xinping Tian, Mengtao Li & Xiaofeng Zeng

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  1. Hanxiao You
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You, H., Xu, D., Zhao, J. et al. JAK Inhibitors: Prospects in Connective Tissue Diseases. Clinic Rev Allerg Immunol 59, 334–351 (2020). https://doi.org/10.1007/s12016-020-08786-6

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