Baricitinib for the treatment of rheumatoid arthritis and systemic lupus erythematosus: a 2019 update

ABSTRACT

Introduction: JAK, which constitutively binds to some cytokine receptors, plays an important role in cytokine signaling. While JAK is comprised of JAK1, JAK2, JAK3, and Tyk2, more than 40 types of cytokines transmit signals through JAK. Baricitinib is reported to be highly effective in the treatment of rheumatoid arthritis (RA) and is the second drug launched as a JAK inhibitor for RA.

Area covered: We provide an overview of the mechanisms of action of baricitinib and its clinical implications in RA and other autoimmune diseases based on recent reports. This review outlines the mechanisms of action of baricitinib on human immune cells, the results of Phase III trials for RA, and the results of Phase II trials on SLE.

Expert opinion: Baricitinib has potential to fine-tune various immune networks through a variety of mechanisms. Precision medicine is required in order to achieve maximum effects of targeted synthetic DMARDs including baricitinib and biological DMARDs in the future.

KEYWORDS:

• Baricitinib
• tofacitinib
• JAK
• STAT
• rheumatoid arthritis

Article highlights

• Baricitinib selectively targets JAK1 and JAK2.

• The efficacy of baricitinib plus MTX exceeded that of adalimumab plus MTX in patients with MTX-inadequate response RA patients.

• In the clinical trial of RA, the efficacy of baricitinib monotherapy exceeded that of MTX monotherapy, while the frequencies of adverse events were comparable in both groups.

• In the clinical trial of SLE, baricitinib showed promising results.

Declaration of interest

S Kubo has received speaking fees from Bristol-Myers, Pfizer, Takeda, and Eli Lilly. Y Tanaka, has received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, Abbvie, YL Biologics, Bristol-Myers, Glaxo-Smithkline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen, Asahi-kasei and has received research grants from Mitsubishi-Tanabe, Bristol-Myers, Eisai, Chugai, Takeda, Abbvie, Astellas, Daiichi-Sankyo, Ono, MSD, Taisho-Toyama. S Nakayamada has received speaking fees from Bristol-Myers, Sanofi, Abbvie, Eisai, Eli Lilly, Chugai, Pfizer, Takeda, and also research grants from Mitsubishi-Tanabe, Novartis and MSD. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Eli Lilly provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This work was supported in part by a Grant-In-Aid for Scientific Research from the Ministry of Health, Labor and Welfare of Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan (JSPS KAKENHI 15K08790, 17K16218), and the University of Occupational and Environmental Health, Japan, through UOEH Grant for Advanced Research.