Drug Treatment of Neuromyelitis Optica Spectrum Disorders: Out with the Old, in with the New?

Neuromyelitis optica spectrum disorders (NMOSD) are rare neuroinflammatory demyelinating diseases of the CNS, mainly affecting optic nerves, spinal cord and brainstem regions. The diagnosis depends on clinical symptoms, MRI findings and the detection of autoantibodies against the water channel aquaporin 4 (AQP4-Ab). This autoantibody is particularly important for diagnostic sensitivity and specificity and further sets the course for major therapeutic decisions. Due to a relapsing course with the accumulation of disability, relapse prevention by immunotherapy is crucial in NMOSD. Until recently, disease-modifying agents specific to NMOSD were not available, and patients were treated with various immunosuppressive drugs and regimens - with variable success. Fortunately, since 2019, three new therapeutic antibodies have entered the market.

We aim to shortly summarise the pathogenesis and biological targets for acute and preventive therapy of adult NMOSD. We will focus on conventional immunotherapies and the recently approved novel biological drugs satralizumab, eculizumab and inebilizumab, and conclude with a brief outlook on future therapeutic approaches.

Although satralizumab, eculizumab and inebilizumab are a breakthrough concerning short-term efficacy, important questions on their future use remain open. There is no data from head-to-head comparisons, and data on long-term safety and efficacy of the new medicines are pending. Whether any of the biologics are efficacious in AQP4-Ab negative NMOSD patients is not yet known - as is how they will succeed in non-responders to conventional immunotherapies. Further, (autoimmune) comorbidities, affordability, and market availability of drugs may be decisive factors for choosing treatments in the near future. We are fortunate to have these new drugs available now, but they will not immediately supersede established off-label drugs in this indication. It is still too early to definitively revise the treatment algorithms for NMOSD - although we are probably on the way.