Bortezomib treatment for severe refractory anti‐NMDA receptor encephalitis

Abstract

ObjectiveTo evaluate the therapeutic potential of bortezomib, a proteasome inhibitor that target plasma cells, in order to revive stalled recovery in patients with anti‐N‐methyl‐d‐aspartate (NMDA) receptor encephalitis who remain bedridden even after aggressive immunotherapy.MethodsWe consecutively enrolled patients with anti‐NMDA receptor encephalitis who remained bedridden after first‐line immunotherapy (steroids and intravenous immunoglobulin), second‐line immunotherapy (rituximab), and tocilizumab treatment, and treated them with subcutaneous bortezomib. Clinical response, functional recovery, and changes in antibody titer in the serum and cerebrospinal fluid were measured.ResultsBefore the bortezomib treatment, the five patients with severe refractory anti‐NMDA receptor encephalitis were in a vegetative state. During the 8 months of follow‐up period, three patients improved to minimally conscious states within 2 months of bortezomib treatment, one failed to improve from a vegetative state. However, no patient achieved functional recovery as measured by the modified Rankin Scale score (mRS). Three patients advanced to a cyclophosphamide with bortezomib and dexamethasone regimen, which only resulted in additional adverse events, without mRS improvement. Among the four patients whose antibody titer was followed, two demonstrated a twofold decrease in the antibody titer in serum and/or cerebrospinal fluid after 2 cycles of bortezomib.InterpretationAlthough there were some improvements in severe refractory patients, clinical response to bortezomib was limited and not clearly distinguishable from the natural course of the disease. The clinical benefit of bortezomib in recent studies requires further validation in different clinical settings.

Early Bortezomib Therapy for Refractory Anti-NMDA Receptor Encephalitis

“…In contrast, in a five-patient case series with historical controls, Shin et al (16) report minimal improvements in clinical symptoms with no improvement in global modified Rankin Scale score following a bortezomib treatment of patients with severe anti-NMDA receptor encephalitis. Moreover, the study population demonstrated a comparable disease course to the historical control group.…”

“…The treatment of refractory anti-NMDA receptor encephalitis represents a clinical challenge as it is often associated with longterm intensive care and significant morbidity (9,13,14,16). Here we describe a patient with a severe course of anti-NMDA receptor encephalitis without immediate response to first-and secondline treatment regimens of steroids, IVIG, plasma exchange, and rituximab.…”

Anti‐N‐methyl‐D‐aspartate receptor encephalitis unresponsive to early and aggressive immunotherapy in a young female: A case report

“…A few studies in literature describe third-line treatments such as bortezomib (a proteasome inhibitor) or tocilizumab (an interleukin-6 receptor antagonist). [13][14][15][16] Our patient had short prodromal symptoms followed by en- brush. [17][18][19] The initial anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score in our patient was 3 (required ICU admission, abnormal MRI, no clinical improvement after 4 weeks of treatment), which aided in the early initiation of second-line immunotherapy.…”

A 24-Year-Old Female With Anti-NMDA Receptor Encephalitis: A Case Report.

“…Finally, for patients with severe and treatment-refractory disease, bortezomib [14] or tocilizumab [15] can be used as third-line therapy.…”