OBJECTIVE: To test the safety of ublituximab, a B cell depleting agent, as add-on therapy in the acute treatment of relapses of neuromyelitis optica spectrum disorder. METHODS: We conducted an open-label phase 1b safety and proof-of-concept trial in 5 subjects with aquaporin-4 (AQP4)-immunoglobulin G (IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD) who presented with acute transverse myelitis and/or optic neuritis. In addition to treating with 1 g of daily intravenous methylprednisolone, we infused a single dose of 450 mg of ublituximab within 5 days of relapse onset. The primary outcome measure was safety, and the secondary efficacy measures included change in Expanded Disability Status Scale (EDSS), durability of remission and B cell counts. RESULTS: Five NMOSD subjects were enrolled, 4 of whom presented with acute transverse myelitis and 1 with acute optic neuritis. Ublituximab proved to be safe in all 5 NMOSD subjects, with no serious adverse events recorded. There were no opportunistic infections in any of the subjects; however, 1 subject experienced a transient leukopenia. EDSS scores dropped from a median of 6.5 on admission to 4.0 on 90-day follow up. Two subjects did not achieve total B cell depletion and relapsed within 3 months. CONCLUSIONS: Ublituximab is a safe add-on therapy for NMOSD patients presenting with acute transverse myelitis and optic neuritis. Preliminary evidence suggests a promising benefit on durability of remission when B cell depletion is achieved. A placebo-controlled trial is necessary to confirm these findings. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with NMOSD with acute transverse myelitis or optic neuritis, ublituximab is safe and may improve neurological outcome.
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