Lupus Nephritis: New and Emerging Biologic and Targeted Therapies

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), a polyclonal systemic autoimmunity directed against nuclear and other self-antigens. SLE/LN affects mostly females during childbearing age, which puts them at risk for the progression of chronic kidney disease (CKD), cardiovascular disease, and pregnancy complications. The current management of LN involves the use of drugs with significant toxicities, and despite many attempts at novel drug interventions, the overall treatment efficacy has remained low. In this article, we discuss recent drug approvals and the upcoming pipeline of novel medications tested in clinical trials to improve effectiveness in terms of LN disease activity, LN relapse, and progression of LN-related CKD. In this context, we discuss (1) drugs with the potential to achieve these treatment goals by modulating SLE activity as the driving force for LN (e.g., belimumab, obinutuzumab, anifrolumab, and others); (2) drugs with SLE-non specific renoprotective effects by targeting non-immune mechanisms of LN progression (dapagliflozin, empagliflozin); and (3) drugs with dual immunosuppressive and antiproteinuric effects (voclosporin). Increasing the number of possible drug options will help to improve the management of LN in terms of efficacy and safety, and enable a more personalized treatment approach.