Chemical JAK inhibitors for the treatment of rheumatoid arthritis

ABSTRACT

Introduction: Considerable advances in the treatment of rheumatoid arthritis (RA) have been made following the advent of biological disease-modifying anti-rheumatic drugs (DMARDs). However, biological DMARDs require intravenous or subcutaneous injection and some patients fail to respond to these drugs or lose their primary response. Currently, Janus kinase (JAK) inhibitors have been developed as a new class of DMARD that inhibits the non-receptor tyrosine kinase family JAK involved in intracellular signaling of various cytokines and growth factors.

Areas covered: Several JAK inhibitors such as tofacitinib and baricitinib are oral synthetic DMARD that inhibit JAK1, 2 and 3. Both drugs have shown feasible efficacy and tolerable safety. In this article, efficacy and adverse events from the phase III trials of JAK inhibitors are overviewed. In addition, pharmacokinetics and mechanism of action of JAK inhibitors in relevance to efficacy and adverse events are covered.

Expert opinion: JAK inhibitors are novel therapies for RA that inhibit multiple cytokines and signaling pathways. Further studies are needed to determine their risk-benefit ratio and selection of the most appropriate patients for such therapy.

KEYWORDS:

• Janus kinase
• Tofacitinib
• Baricitinib
• Rheumatoid arthritis

Article Highlights

• JAK inhibitors are new therapies for rheumatoid arthritis.

• JAK inhibitors are effective in poor responders to other biologics.

• Surveillance data are required for proper assessment of risk of infection and malignancy in patients treated with JAK inhibitors.

This box summarizes key points contained in the article.

Acknowledgments

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

Declaration of interest

Y. Tanaka, has received consulting fees, speaking fees, and/or honoraria from Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers Squibb, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, GlaxoSmithKline and has received research grants from Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, Eisai. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Additional information

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.

Notes on contributors

Shingo Nakayamada

S Nakayamada, Y Tanaka contributed to the overall review and writing of the manuscript. All authors read and approved the final manuscript.