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  • Review Article
  • Published:

Future prospects in biologic therapy for systemic lupus erythematosus

Nature Reviews Rheumatology volume 9, pages 705–720 (2013)Cite this article

Subjects

Key Points

  • B cells, T cells and cytokines are key in the pathogenesis of systemic lupus erythematosus (SLE), and numerous biologic agents that target these cells and factors are in various stages of development

  • B-cell-directed biologic therapies include agents targeting CD20, CD19, CD22, CD40, and FcγRIIb, and some of these agents have already shown promising results

  • T-cell-directed biologic agents are aimed at promoting T cell tolerance, blocking T cell activation and differentiation, altering T cell trafficking, or generating regulatory T cells

  • Cytokine-directed biologic therapies include agents targeting BAFF, type I interferons, IL-6, and TNF, with an anti-BAFF monoclonal antibody (belimumab) already approved by the FDA for treatment of SLE

Abstract

With the approval by the FDA in 2011 of a biologic agent (namely belimumab) for the treatment of systemic lupus erythematosus (SLE), optimism abounds that additional biologic (and nonbiologic) agents will be similarly endorsed. Given the numerous immune-based abnormalities associated with SLE, the potential therapeutic targets for biologic agents and the candidate biologic approaches are also numerous. These approaches include: biologic agents that promote B-cell depletion, B-cell inactivation, or the generation of regulatory B cells; biologic agents that induce T-cell tolerance, block T-cell activation and differentiation, or alter T-cell trafficking; biologic agents that target the B-cell activating factor (BAFF) axis, type I interferons, IL-6 and its receptor, or TNF; and the adoptive transfer of ex vivo-generated regulatory T cells. Owing to the great heterogeneity inherent to SLE, no single approach should be expected to be effective in all patients. As our understanding of the pathogenic mechanisms of SLE continues to expand, additional therapeutic targets and approaches will undoubtedly be identified and should be fully exploited.

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Figure 1: Selective versus 'shotgun' targeting of B cells.
Figure 2: Mimicking of immune-complex-mediated inhibition of B cell activation by genetically engineered mAbs.
Figure 3: T cell inhibition at multiple stages.
Figure 4: The BAFF axis and its inhibition.

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Acknowledgements

The author's research is funded in part by a grant from the Alliance for Lupus Research.

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  1. Division of Rheumatology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, HMR 711, Los Angeles, 90033, CA, USA

    William Stohl

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The author declares that he is a member of a scientific advisory board for Eli Lilly, has consulted for Novartis, and has received preclinical grant support from Xencor.

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Stohl, W. Future prospects in biologic therapy for systemic lupus erythematosus. Nat Rev Rheumatol 9, 705–720 (2013). https://doi.org/10.1038/nrrheum.2013.136

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