State-of-the-art treatment of systemic lupus erythematosus

Abstract

As glucocorticoids and immunosuppressive drugs are non-specific therapeutic agents that cause many adverse reactions, the development of biologicals aiming to control specific molecular targets is anticipated for the treatment of systemic lupus erythematosus (SLE). The antibody targeting B cell-activating factor belonging to the tumor necrosis factor family (BAFF) belimumab was the first biological approved for SLE. At present, many biologicals, such as anifrolumab (anti-type I interferon receptor antibody) and ustekinumab (antibody against interleukin 12/23 [p40]), are in clinical trials. Thus, successful treatments with biologicals targeting "bridging cytokines" produced by dendritic cells, which form a bridge between the innate and acquired immune/autoimmune systems, is of particular interest. Moreover, a phase IIb clinical trial of baricitinib, a low-molecular-weight compound targeting Janus kinase 1/2, in patients with SLE revealed that baricitinib was significantly more effective for relieving arthritis and skin manifestations than placebo, and the trial met the primary endpoint. In the future, it is expected that drugs with better efficacy and safety profiles will be used to apply therapeutic strategies, such as precision medicine, in which different molecular target drugs are used for patients classified by their conditions, and to set a therapeutic goal of the discontinuation of glucocorticoids.

Keywords: JAK inhibitor; biological; innate immunity; systemic lupus erythematosus; treatment.

FIGURE 1

The development of biologicals for the treatment of systemic lupus erythematosus. Some of them have already failed in clinical trials

FIGURE 2

“Bridging cytokines” in systemic lupus erythematosus (SLE). Bridging cytokines produced by dendritic cells, which form a bridge between the innate and acquired immune/autoimmune systems would be targets for treatment by biologicals in SLE

FIGURE 3

Potential for precision medicine in rheumatic diseases and systemic autoimmune diseases. Shown is an example of possible precision medicine for psoriatic arthritis using different biologicals based on immune phenotypic analysis of peripheral lymphocytes