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Recent Progress in JAK Inhibitors for the Treatment of Rheumatoid Arthritis

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An Erratum to this article was published on 03 October 2016

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation and joint destruction. Considerable advance in the treatment of RA has been made following the advent of biological disease-modifying anti-rheumatic drugs (DMARDs). However, these biologics require intravenous or subcutaneous injection and some patients fail to respond to biological DMARDs or lose their primary response. Various cytokines and cell surface molecules bind to receptors on the cell surface, resulting in the activation of various cell signaling pathways, including phosphorylation of kinase proteins. Among these kinases, the non-receptor tyrosine kinase family Janus kinase (JAK) plays a pivotal role in the pathological processes of RA. Several JAK inhibitors have been developed as new therapies for patients with RA. These are oral synthetic DMARDs that inhibit JAK1, 2, and 3. One JAK inhibitor, tofacitinib, has already been approved in many countries. Results of phase III clinical trials using a JAK1/2 inhibitor, baricitinib, have shown feasible efficacy and tolerable safety. Both drugs are effective in patients who showed inadequate response to biological DMARDs as well as synthetic DMARDs. In addition, clinical phase III trials using filgotinib and ABT-494, specific JAK1 inhibitors, are currently underway. JAK inhibitors are novel therapies for RA, but further studies are needed to determine their risk–benefit ratio and selection of the most appropriate patients for such therapy.

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Acknowledgments

The authors thank all medical staff in all participating institutions for providing the data.

Contributors

SN and YT contributed to overall review and writing of the manuscript. All authors read and approved the final manuscript.

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  1. The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu, 807-8555, Japan

    Shingo Nakayamada, Satoshi Kubo, Shigeru Iwata & Yoshiya Tanaka

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  1. Shingo Nakayamada
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  2. Satoshi Kubo
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Correspondence to Yoshiya Tanaka.

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Funding

This work was supported in part by Research on Rare and Intractable Diseases and Research Grant-In-Aid for Scientific Research by the Ministry of Health, Labor and Welfare of Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the University of Occupational and Environmental Health, Japan, and UOEH Grant for Advanced Research.

Conflict of interest

Y Tanaka has received consulting fees, lecture fees, and/or honoraria from Mitsubishi-Tanabe, Eisai, Chugai, Abbott Japan, Astellas, Daiichi-Sankyo, Abbvie, Janssen, Pfizer, Takeda, Astra-Zeneca, Eli Lilly Japan, GlaxoSmithKline, Quintiles, MSD, Asahi-Kasei and has received research grants from Bristol-Myers, Mitsubishi-Tanabe, Abbvie, MSD, Chugai, Astellas, and Daiichi-Sankyo. S. Nakayamada, S. Kubo and S. Iwata declare no conflict of interest.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s40259-016-0198-x.

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Nakayamada, S., Kubo, S., Iwata, S. et al. Recent Progress in JAK Inhibitors for the Treatment of Rheumatoid Arthritis. BioDrugs 30, 407–419 (2016). https://doi.org/10.1007/s40259-016-0190-5

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