Bortezomib for anti-NMDAR encephalitis following daclizumab treatment in a patient with multiple sclerosis

Abstract

BackgroundDaclizumab is an anti-CD25 monoclonal antibody developed for the treatment of relapsing remitting multiple sclerosis, which was withdrawn worldwide in March 2018, due to emerging serious immune-mediated systemic andcentral nervous system adverse events. We report a case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis occurring 14 weeks after stopping daclizumab, which responded to the proteasome inhibitor bortezomib.MethodsFollowing lack of effective clinical response to first line (corticosteroid, plasma exchange, intravenous immunoglobulin) and second line (rituximab) treatments, bortezomib therapy was commenced. The patient received six cycles of bortezomib treatment.ResultsClinical improvement was noted 4 weeks after the first of six cycles of bortezomib and the patient experienced sustained clinical improvement.ConclusionOur case provides further class IV evidence of the use of bortezomib therapy for treatment refractory anti-NMDAR encephalitis.

Overlapping anti-NMDAR encephalitis and multiple sclerosis: A case report and literature review

“…Overlapping anti-NMDAR encephalitis and MS have been reported in 15 cases. We summarized the clinical features of these patients and present them in Table 1 , including five from England ( 6 , 11 , 12 , 18 ), two from Germany ( 8 , 10 ), one from Japan ( 7 ), one from Austria ( 9 ), one from Istanbul ( 14 ), one from Italy ( 15 ), one from Canada ( 17 ), one from Iran ( 19 ), and two from China ( 13 , 16 ). Among the 15 patients, the male-to-female ratio was 2:1.…”

Therapeutic Approach to Autoimmune Neurologic Disorders

“…Case reports of patients with treatment-refractory NMDA receptor encephalitis have suggested a possible benefit in the use of bortezomib, but these reports are complicated by concomitant use of other immunotherapies. [76][77][78][79] Additional studies are needed to better understand whether the clinical improvement in these patients represents the natural history of this disease or whether bortezomib treatment was responsible for this clinical improvement. The Generate-Boost (A Multicenter Randomized, Controlled, Double-blinded Trial to Evaluate Efficacy and Safety of Bortezomib in Patients With Severe Autoimmune Encephalitis) clinical trial 80 will investigate the role of bortezomib in the treatment of severe autoimmune encephalitis.…”

“…Bortezomib is an inhibitor of the 26S proteasome, which has been used for the treatment of mantle cell lymphoma and multiple myeloma for nearly 2 decades. Case reports of patients with treatment-refractory NMDA receptor encephalitis have suggested a possible benefit in the use of bortezomib, but these reports are complicated by concomitant use of other immunotherapies 76-79 . Additional studies are needed to better understand whether the clinical improvement in these patients represents the natural history of this disease or whether bortezomib treatment was responsible for this clinical improvement.…”

Treatment Options in Refractory Autoimmune Encephalitis

“…As for AEs, treatment with bortezomib has been nearly exclusively reported in patients with anti-NMDAR encephalitis, in particular, in cases with severe disability who required a prolonged intensive care unit stay at the time of treatment administration, and in one patient with CASPR2 encephalitis, unsuccessfully treated with three cycles [38,39]. In the reported single cases or small case series, bortezomib was used after failure of conventional or unconventional treatments such as cyclophosphamide, rituximab, interleukin-2, or tocilizumab [39][40][41][42][43][44][45][46][47][48][49][50][51][52]. As expected, bortezomib has been shown to deplete antibody-secreting cells that were not susceptible to rituximab [52].…”