Novel JAK inhibitors under investigation for systemic lupus erythematosus: - where are we now?

ABSTRACT

Introduction

Glucocorticoids and immunosuppressants are used to treat systemic lupus erythematosus (SLE). However, patients with SLE have poor long-term prognoses. This can be attributed to organ damage caused by flare-ups and drug toxicity due to the administration of nonspecific treatment. Therefore, SLE should be treated using therapeutic agents specific to its pathology. Janus kinase (JAK) inhibitors exert multitargeted effects by blocking the signaling of multiple cytokines. The use of JAK inhibitors has been approved to treat several inflammatory autoimmune diseases. Several clinical trials of JAK inhibitors for SLE treatment are ongoing.

Area covered

This review summarizes the basic and clinical significance of JAK inhibitors for treating SLE and the current status of the development of JAK inhibitors based on recent reports.

Expert opinion

SLE is a clinically and immunologically heterogeneous disease. Therefore, drugs targeting a single molecule require precision medicine to exert maximal therapeutic efficacy. JAK inhibitors can probably fine-tune the immune network via various mechanisms and broadly regulate complex immune-mediated pathologies in SLE. However, evidence is required to address some safety concerns associated with the use of JAK inhibitors in patients with SLE, including infections (particularly herpes zoster) and thromboembolism (particularly in the presence of concomitant antiphospholipid syndrome).

KEYWORDS:

• JAK inhibitor
• molecular targeted therapy
• T cell
• B cell
• systemic lupus erythematosu

Article highlights

• Abnormalities in both innate and acquired immunity resulting from many cytokines are involved in the development of SLE.

• JAK is involved in various immunological abnormalities, and thus, it is an attractive therapeutic target for SLE.

• Multiple clinical trials on JAK inhibitors that differ in the selectivity for JAK family proteins for the treatment of SLE are being conducted.

Declaration of interest

S Nakayamada has received consulting fees, lecture fees, and/or honoraria from Bristol-Myers, GlaxoSmithKline, Chugai, Sanofi, Pfizer, Astellas, Asahi-kasei, Boehringer Ingelheim and has received research grants from Mitsubishi-Tanabe, Novartis, and MSD. Y Tanaka has received lecture fees and/or honoraria from Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, AbbVie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, research grants from AbbVie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, Daiichi-Sankyo and consultation fees from Eli Lilly, Daiichi-Sankyo, Taisho, Ayumi, Sanofi, GSK, AbbVie.

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.

Acknowledgments

We thank Crimson Interactive Pvt. Ltd. (Ulatus) – www.ulatus.jp for their assistance in manuscript translation and editing.

Additional information

Funding

This work was supported in part by a Japan Society for the Promotion of Science (JSPS) KAKENHI (grant number JP20K08815) and the University of Occupational and Environmental Health, Japan through an UOEH Grant for Advanced Research (grant number H30-905).