Novel and emerging treatment strategies for lupus nephritis

Lupus nephritis (LN) is a key predictor for kidney failure and death in patients with systemic lupus erythematosus. While conventional immunosuppressive treatments have improved the outcome of LN, novel therapies continue to emerge. These new agents targetspecific immune-reactive cells, cytokines and signaling pathways in LN pathogenesis.New therapeutic approaches that target B cells, T cells, crucial cytokines and their signaling pathways in LN.Although earlier studies of rituximab fail to show benefit, a newer generation anti-CD20 biologic, obinutuzumab, is promising in LN. Inhibition of B-cell activating factor by belimumab confers superior renal response when added to the standard of care (SOC) regimens, leading to its recent approval for LN. Therapies targeting plasma cells (proteasome inhibitors, anti-CD38) in LN are being developed. A newer generation calcineurin inhibitor, voclosporin, when combined with SOC, results in better renal responses in LN. Other innovative strategies include targeting type I interferon, co-stimulatory signals, complement cascade (anti-C5b) and intracellular proliferation signals (e.g. mTOR, JAK1/2, BTK). While these novel agents improve the short-term renal responses without increased toxicities, long-term data on disease progression and safety remain to be established. Patient stratification by clinical phenotypes, biomarkers and molecular profiles helps enhance the efficacy and cost-effectiveness of novel therapies of LN.