Advances in the Treatment of Neuromyelitis Optica Spectrum Disorders

Neuromyelitis optica spectrum disorder (NMOSD) encompasses inflammatory central nervous system diseases, in which severe relapses of demyelination may result in significant long-term neurologic disability. Recently, three novel immunotherapies have emerged with positive results from phase III randomized trials for relapse reduction in NMOSD. Eculizumab (complement inhibitor) added to stable immunosuppressant therapy significantly reduced the risk of relapse in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD when compared with addition of placebo, but did not demonstrate a change in disability outcomes. Inebilizumab (anti-CD19 antibody targeting B cells) monotherapy significantly increased the time to first NMOSD attack when compared with placebo, and conferred favorable disability outcomes (reduction in disability progression) and fewer NMOSD-associated inpatient hospitalizations. Satralizumab (interleukin-6 receptor inhibitor), added to baseline immunosuppressant therapy, lowered the risk of NMOSD relapse, when compared with adding to placebo, in a study including adolescents. Safety signals emerged in each trial, including rare deaths in the eculizumab and inebilizumab trials. Individual selection of the best preventative therapy for patients will require careful consideration of several factors including AQP4-IgG serostatus, previous immunotherapies, medical comorbidities, and physician and patient preferences. Further work is needed to determine long-term efficacy and safety, but these immunotherapies have formally expanded the armamentarium for treatment of this rare and severe central nervous system neuroinflammatory disorder.