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Abstract
The treatment of lupus nephritis (LN) in recent decades has relied on combined treatment with corticosteroids and either mycophenolate mofetil (MMF) or intravenous boluses of cyclophosphamide. In recent years the therapeutic possibilities for LN have expanded remarkably, thanks to the completion of several landmark randomised controlled trials (RCT) that have demonstrated the efficacy of new drugs. Drugs that have shown efficacy in the initial treatment of LN include calcineurin inhibitors (CNI). Several small local trials with cyclosporine and tacrolimus showed that these CNI increase the achievement of remission and have a strong antiproteinuric effect. Recently, the AURORA-1 study confirmed that voclosporin, a new CNI, added to corticosteroids and MMF was superior to placebo in obtaining complete remission with a good safety profile.1 Longer-term follow-up of patients suggests that voclosporin does not share the nephrotoxic effect of other CNIs. Belimumab, a drug that blocks BLyS (a stimulator of B lymphocyte proliferation), had shown efficacy in improving different extrarenal manifestations of systemic lupus erythematosus (SLE) and decrease immunological activity. The BLYS-LN study demonstrated that belimumab, added to corticosteroids and MMF, induces a significantly higher number of LN remission than placebo, with a satisfactory safety profile.2 Obinutuzumab, a newer anti-CD20 drug, has also shown encouraging preliminary data as initial therapy for NL. It is important to highlight that all these recent RCT compare triple therapy (corticosteroids plus MMF and the new drug under evaluation) with double therapy (corticosteroids plus MMF and placebo), so the addition of a CNI or belimumab for refractory cases or the use of triple therapy regimens from the onset for patients with high-risk profiles are recommended in recent guidelines.3 Conversely, new renoprotective and cardioprotective drugs, such as SGLT2 inhibitors, are starting to show their importance in the non-immunosuppressive treatment of LN.4 Despite these important successes in improving the initial treatment of LN, more studies are needed to determine the optimal maintenance treatment and criteria to personalize treatment duration in patients who achieve remission.
References
Rovin BH, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021 May 29;397(10289):2070–2080. doi: 10.1016/S0140-6736(21)00578-X. Epub 2021 May 7. Erratum in: Lancet. 2021 May 29;397(10289):2048.
Furie R, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med. 2020 Sep 17;383(12):1117–1128. doi: 10.1056/NEJMoa2001180.
Rojas-Rivera JE, et al. Consensus document of the Spanish group for the study of the glomerular diseases (GLOSEN) for the diagnosis and treatment of lupus nephritis. Nefrologia (Engl Ed). 2023 Jan-Feb;43(1):6–47. doi: 10.1016/j.nefroe.2023.05.006.
Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020 Oct 8;383(15):1436–1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.
Learning Objectives
Describe studies about the use of calcineurin inhibitors in LN
Describe the use of belimumab in LN
Discuss the option of triple versus double therapy as initial treatment in LN
Discuss different treatment options according to a patient´s disease profile
Discuss newer non-immunosuppressive treatments for renal and cardioprotection in LN
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