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Bortezomib is efficacious in the treatment of severe childhood-onset neuropsychiatric systemic lupus erythematosus with psychosis: a case series and mini-review of B-cell immunomodulation in antibody-mediated diseases

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Abstract

Childhood-onset neuropsychiatric systemic lupus erythematosus (cNPSLE) with psychosis is a challenging manifestation of SLE. Pathogenic long-lived plasma cells (LLPCs) are not specifically targeted by standard immunosuppression and their persistence contributes to chronic autoimmunity. Bortezomib is approved for the treatment of multiple myeloma and has shown benefits in a variety of other antibody-mediated diseases. Bortezomib may be efficacious for severe or treatment-refractory cNPSLE through eradication of LLPCs, decreasing autoantibody production. We describe the first pediatric case series of five patients with unrelenting cNPSLE with psychosis who were treated safely and effectively with bortezomib between 2011 and 2017. Most patients had persistent cNPSLE with psychosis despite aggressive immunosuppression with methylprednisolone, cyclophosphamide, rituximab, and usually plasmapheresis. All patients demonstrated rapid clinical improvement in their psychotic manifestations with the ability to quickly taper immunosuppression after the introduction of bortezomib. No patient had a recurrence of overt psychosis during a follow-up period of 1–10 years. Secondary hypogammaglobulinemia developed in all five patients and required immunoglobulin replacement. No other severe side effects or adverse events were observed. Bortezomib-mediated LLPC depletion is a promising therapy for severe recalcitrant cNPSLE with psychosis when used as adjunctive therapy to conventional immunosuppression, B-cell, and antibody-depleting therapies. After initiation of bortezomib, patients had rapid, demonstrable improvement in psychosis as well as reduction in glucocorticoids and antipsychotics. Further investigation is needed to determine the therapeutic role of bortezomib in severe cNPSLE and cSLE. We present a mini-review of the rationale for bortezomib use and novel B-cell immunomodulation in rheumatic disease.

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The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available.

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Acknowledgements

We would like to thank our advanced practice registered nurses and administrative staff in the Division of Pediatric Allergy, Immunology, and Rheumatology at the University of Florida, Gainesville, who helped facilitate the care of these complex patients.

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  1. Akaluck Thatayatikom

    Present address: Department of Pediatrics, Division of Rheumatology and Immunology, AdventHealth for Children, Orlando, FL, USA

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  1. Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, University of Florida, Gainesville, FL, USA

    Renee F. Modica, Akaluck Thatayatikom, Denise H. Bell-Brunson & Melissa E. Elder

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All authors contributed to the study’s conception and design. Material preparation, data collection, analysis, and literature search were performed by Renee Modica, Akaluck Thatayatikom, Denise Heather Bell-Brunson, and Melissa Elder. The first draft of the manuscript was written in full by Renee Modica and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Modica, R.F., Thatayatikom, A., Bell-Brunson, D.H. et al. Bortezomib is efficacious in the treatment of severe childhood-onset neuropsychiatric systemic lupus erythematosus with psychosis: a case series and mini-review of B-cell immunomodulation in antibody-mediated diseases. Clin Rheumatol 42, 1965–1979 (2023). https://doi.org/10.1007/s10067-023-06559-y

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