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Recent advances in immunotherapies for lupus nephritis

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Abstract

Childhood-onset systemic lupus erythematosus (SLE) is characterized by increased rates of kidney involvement, termed lupus nephritis. Despite the significant morbidity and mortality associated with this disease, lupus nephritis trials have been plagued by repeated failures to meet clinical endpoints. However, improvements in trial design and the development of targeted approaches have begun to yield promising results, including two new FDA-approved lupus nephritis treatments since 2020. These include belimumab, a monoclonal antibody targeting the B cell survival cytokine BAFF (B cell activating factor), and voclosporin, a cyclosporin analog with improved pharmacokinetic characteristics. In this review, we will summarize the data supporting regulatory approval for these agents in lupus nephritis and highlight ongoing clinical trials targeting the diverse immunologic drivers of renal inflammation in SLE. While pediatric patients remain underrepresented in lupus clinical trials, given the increased severity of childhood-onset SLE and need for long-term protection from kidney damage, we anticipate the need for off-label use of these targeted therapies in the pediatric population. Future studies are needed to define optimal patient selection, drug combinations, and treatment duration in pediatric lupus nephritis.

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Funding

This work was supported by the National Institutes of Health under award numbers: R01AR073938 (SWJ), R01AR075813 (SWJ), 5T32DK007662 (MK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support provided by the Arthritis National Research Foundation (ANRF) Eng Tan Scholar Award (SWJ); and by a Lupus Research Alliance, Novel Research Grants (SWJ). Figures were created with BioRender.com.

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  1. Division of Pediatric Nephrology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA

    Machi Kaneko & Shaun W. Jackson

  2. Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA

    Shaun W. Jackson

  3. Seattle Childrens Research Institute, 1900 Ninth Avenue, M/S JMB-6, WA, 98101, Seattle, USA

    Shaun W. Jackson

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1. E; 2. C; 3. A; 4. B; 5. B

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Kaneko, M., Jackson, S.W. Recent advances in immunotherapies for lupus nephritis. Pediatr Nephrol 38, 1001–1012 (2023). https://doi.org/10.1007/s00467-022-05670-7

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  • DOI: https://doi.org/10.1007/s00467-022-05670-7

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