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  • Review Article
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New therapies for systemic lupus erythematosus — past imperfect, future tense

Nature Reviews Rheumatology volume 15, pages 403–412 (2019)Cite this article

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An Author Correction to this article was published on 03 July 2019

This article has been updated

Abstract

The failure of many new, mostly biologic, drugs to meet their primary end points in double-blind clinical trials in patients with systemic lupus erythematosus (SLE) has caused a profound sense of disappointment among both physicians and patients. Arguably, the success of B cell depletion with rituximab in open-label studies and in patients with lupus nephritis in the USA and in difficult-to-treat patients with SLE in the UK, together with the approval of belimumab (which blocks B cell-activating factor (BAFF)) for use in patients with SLE and the recognition that clinical trial design can be improved, have given some cause for hope. However, changes to therapies in current use and the development of new approaches are urgently needed. The results of the latest studies investigating the use of several new approaches to treating SLE are discussed in this Review, including: fully humanized anti-CD20 and anti-CD19 monoclonal antibodies; inhibition of tyrosine-protein kinase BTK; CD40 ligand blockade; interfering with the presentation of antigen to autoreactive T cells using a peptide approach; a receptor decoy approach using an analogue of Fcγ receptor IIB; dual blockade of IL-12 and IL-23; and inhibition of Janus kinases.

Key points

  • The approval of new therapies, especially biologic drugs, for systemic lupus erythematosus (SLE) has been scarce in comparison to rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

  • Belimumab (FDA approved) and rituximab (National Health Service England approved) are available for use in some countries, although the cost (particularly of belimumab) mitigates their universal uptake.

  • Clinical trial design for SLE is problematic, and success in phase II trials is not often followed by success in phase III trials.

  • Several new approaches are under investigation that target B cells, cytokines or intracellular signalling pathways, providing hope that new therapies will be approved for SLE.

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Fig. 1: Therapeutic targets in systemic lupus erythematosus.

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  • 03 July 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

D.A.I. acknowledges the support of the Biomedical Research Centre award to University College Hospital and University College London.

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  1. Department of Rheumatology, Cork University Hospital, Cork, Ireland

    Grainne Murphy

  2. Centre for Rheumatology/Division of Medicine, University College London, London, UK

    David A. Isenberg

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D.A.I. declares that he has received honoraria from AstraZeneca, Celgene, Eli Lilly, Merck Serono, Roche, UCB and XTL Biopharmaceuticals. G.M. declares no competing interests.

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Murphy, G., Isenberg, D.A. New therapies for systemic lupus erythematosus — past imperfect, future tense. Nat Rev Rheumatol 15, 403–412 (2019). https://doi.org/10.1038/s41584-019-0235-5

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