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Review
. 2022 Nov 30;18(5):2072143.
doi: 10.1080/21645515.2022.2072143. Epub 2022 May 19.

Belimumab for systemic lupus erythematosus - Focus on lupus nephritis

Marlene Plüß  1 , Silvia Piantoni  2 , Björn Tampe  1 , Alfred H J Kim  3   4   5 , Peter Korsten  1
Affiliations
Review

Belimumab for systemic lupus erythematosus - Focus on lupus nephritis

Marlene Plüß et al. Hum Vaccin Immunother. .

Abstract

In recent years, advances in the treatment and management of patients with systemic lupus erythematosus (SLE) have improved their life expectancy and quality of life. However, lupus nephritis (LN) still represents a major life-threatening complication of the disease. Belimumab (BEL), a fully human monoclonal IgG1λ antibody neutralizing soluble B cell activating factor, was approved more than ten years ago as add-on therapy in adults and pediatric patients with a highly active, autoantibody-positive disease despite standard of care (SoC). Recently, the superiority of the addition of BEL to SoC was also demonstrated in LN. In this review, we provide a comprehensive overview of the study landscape, available therapeutic options for SLE (focusing on BEL in renal and non-renal SLE), and new perspectives in the treatment field of this disease. A personalized treatment approach will likely become available with the advent of novel therapeutic agents for SLE and LN.

Keywords: Systemic lupus erythematosus; belimumab; immunosuppressives; lupus nephritis.

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Conflict of interest statement

M.P. reports no conflicts of interest. S.P. has received honoraria or travel support from Abbvie, Astra Zeneca, Bristol-Myers-Squibb, Galapagos, Janssen-Cilag, and Pfizer, all unrelated to this paper. B.T. reports no conflicts of interest. A.H.J.K. participated in consulting, advisory board, or speaker’s bureau for Alexion Pharmaceuticals, AstraZeneca, Aurinia Pharmaceuticals, Exagen Diagnostics, Inc., GlaxoSmithKline, and Pfizer and received funding under a sponsored research agreement unrelated to this review from GlaxoSmithKline and Foghorn Therapeutics. P.K. has received honoraria or travel support from Abbvie, Amgen, Biogen, Boehringer Ingelheim, Bristol-Myers-Squibb, Chugai, Gilead, GlaxoSmithKline, Janssen-Cilag, Lilly, Pfizer, and Sanofi-Aventis, all unrelated to this paper. P.K. received research grants from GlaxoSmithKline and Diamed Medizintechnik GmbH, unrelated to this paper. P.K. also discloses his participation as an investigator in the BLISS-LN trial. GlaxoSmithKline, the manufacturer of belimumab, had no role in the conceptualization, data acquisition, data interpretation, or writing of this paper.

Figures

Figure 1.
Figure 1.
Main mechanisms of action of commonly used and selected promising drugs in Lupus nephritis. The upper part shows the extracellular mechanisms of action of the drugs, and the lower part the intracellular target structures and main cell types involved. Belimumab acts by blocking Bcell activating factor (BAFF) and subsequent inhibition of binding to its receptors (BAFF-R, TACI, BCMA) which are expressed on Band Tcells, thus decreasing antibody production and interfering with Tcell functions. Rituximab is achimeric mouse-human type Iantibody, and obinutuzumab is a humanized type II antibody that act by inhibition of cluster of differentiation (CD) 20 on B cells inducing cell death. They promote complement (C)-dependent cytotoxicity, antibody-dependent cellular toxicity, and antibody-dependent phagocytosis. The first mechanism is prevalent for rituximab, the others for obinutuzumab. Both traditional agents, mycophenolate mofetil and cyclophosphamide, are pro-drugs that are converted intracellularly to their active compounds with subsequent B and T cell apoptosis. Anifrolumab is anovel anti-interferon alpha receptor subunit 1 antibody (IFNAR1), which blocks downstream interferon pathways affecting B, T, epithelial, and dendritic cells. Voclosporin and tacrolimus act similarly as calcineurin inhibitors with subsequent effects on interleukin (IL)-2 inhibiting Tcell proliferation. Another effect is provided by the stabilization of the podocyte cytoskeleton. Created with biorender.com.
Figure 2.
Figure 2.
Timeline of milestone belimumab Phase I-IV trials, including post hoc analyses. The respective study phases are color-coded. The boxes show the first author and the name of the trial, if available. In addition, the main primary and secondary outcome measures are reported.
See this image and copyright information in PMC

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