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.