Pathological relevance and treatment perspective of JAK targeting in systemic lupus erythematosus

ABSTRACT

Introduction

The pathogenesis of systemic lupus erythematosus (SLE) involves abnormalities in both acquired and innate immune system, which is mediated by numerous cytokines. Janus kinase (JAK) plays important roles in the signaling pathways of those cytokines and is an attractive therapeutic target for SLE. Currently, multiple clinical trials using JAK inhibitors with different selectivities for JAK family proteins are being conducted in SLE.

Area covered

In this article, we provide an overview of the pathological relevance of JAK and the clinical implications of JAK inhibitors in SLE based on recent reports.

Expert opinion

JAK inhibitors have the potential to modulate various immune networks through a variety of mechanisms, potentially regulating the complex immunopathogenesis in SLE. SLE is a clinically and immunologically heterogeneous disease; therefore, precision medicine is required to maximize the efficacy of JAK inhibitors. Further studies are needed to determine their risk-benefit ratio and selection of the most appropriate patients for JAK inhibitors.

KEYWORDS:

• Glucocorticoids
• JAK inhibitor
• lymphocyte
• molecular targeted therapy
• systemic lupus erythematosus

Article highlights

• Pathogenesis of SLE involves abnormalities in both acquired and innate immune system, which are mediated by numerous cytokines.

• JAKs are involved in diverse immune abnormalities and are an attractive therapeutic target for SLE.

• Multiple SLE clinical trials using JAK inhibitors with different selectivities for JAK family proteins are being conducted.

• Precision medicine may be required to maximize the efficacy of JAK inhibitors in patients with SLE.

Conflict 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 disclose

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary Material

Supplemental data for this article can be accessed here

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 (#JP20K08815, JSPS KAKENHI), and a grant from the University of Occupational and Environmental Health, Japan, through UOEH Grant for Advanced Research.