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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS), primarily affecting the optic nerves and spinal cord. It was originally considered a variant of multiple sclerosis, Waliszewska-Prosół et al wrote in their study on NMOSD treatment.

Our understanding of NMOSD has since evolved. “Only in 2004, with the discovery of specific [immunoglobulin G (IgG)] antibodies directed against aquaporin-4, considered as pathognomonic for NMO, did it become possible to classify this disorder as a separate entity,” the researchers explained.

As a result of recent advancements in our knowledge about NMOSD, we have begun to observe the emergence of new treatments that have the potential to significantly improve patient outcomes. We will be discussing some of these novel therapies in this article.

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Conventional Therapies

Aquaporin-4 IgG is such a specific biomarker for this disease that seropositivity for this biomarker in the context of an inflammatory attack on the CNS is enough for physicians to diagnose NMOSD, especially when the spinal cord and the optic nerves are specifically involved.

Levy and colleagues, in their study on new therapies for NMOSD, wrote about the significance of this biomarker: “The discovery of aquaporin-4 IgG prompted research into how the immune system causes astrocyte damage and led to the identification of crucial immunological targets, among which were the terminal complement system, the interleukin-6 (IL-6) receptor, and B cells.”

Conventionally, immunosuppressive therapies have been used to treat NMOSD. Waliszewska-Prosół et al wrote, “Although not officially approved and mostly used on an empirical basis or tested in short-term, open-label trials, a few immunosuppressants have been applied in NMO as a single or combined therapy.” Among the most common immunosuppressants used are azathioprine, mitoxantrone, methotrexate, and mycophenolate mofetil. 

These conventional immunosuppressive therapies have proved advantageous to NMOSD patients over the years. “Conventional immunosuppressive therapies have been used for prevention of relapses out of license because of their effectiveness in other antibody-mediated conditions and because they appear to provide some benefit to people with NMOSD,” Levy et al commented.

However, despite their role in improving clinical outcomes in NMOSD patients, it should be noted that consensus treatment recommendations for immunosuppressants are based on a few observational clinical studies that did not include masking or control groups. 

New Agents Bring New Approaches  

Levy and colleagues conducted a literature review of studies investigating the efficacy of 3 new immunosuppressive agents: eculizumab, satralizumab, and inebilizumab. The drugs were approved by the US Food and Drug Administration (FDA) in 2019 and 2020. Each one targets the immune system in a different way. 


Eculizumab works by targeting the complement system. What does the complement system have to do with NMOSD? Waliszewska-Prosół et al explained that the complement cascade engages in the inflammatory injury of astrocytes and neurons. This makes it an excellent target for immunosuppressive therapies.

Levy et al reported, “Human clinical trials of a C1-esterase inhibitor to mitigate complement-mediated damage in acute relapses in patients with NMOSD showed a modest benefit, suggesting that complement-mediated activity is contributing to the active inflammatory lesion.”

Another study found that it reduced the median number of relapses from 3 per year to zero, significantly improving the quality of life of NMOSD patients. 


Satralizumab is a monoclonal antibody that works by targeting the IL-6 receptor. IL-6 contributes to the inflammatory processes in NMOSD patients through 4 main mechanisms: aiding in the differentiation of naive T cells from proinflammatory T-helper-17 cells, preventing the activation of regulatory T cells, stimulating aquaporin-4-IgG-producing plasmablasts, and causing the innate immune response to become active.

Waliszewska-Prosół et al reported, “Two phase 3, double-blind, randomized multicenter trials have demonstrated beneficial effects of satralizumab upon NMO clinical course when used as an additive treatment to baseline low-dose immunosuppressants (SAkuraSky) or as a monotherapy (SAkuraStar).” 


Inebilizumab is a monoclonal antibody targeting the B-lymphocyte antigen CD19. It has the dual function of depleting B cells and removing from circulation B-cell precursors and plasmablasts. It was created based on rituximab, which has been shown to drastically cut the risk of relapse among some NMOSD patients.

As with eculizumab and satralizumab, clinical trials point to its promise and potential. Waliszewska-Prosół and colleagues summarized a landmark trial involving inebilizumab, writing, “In a phase-3 double-blind, randomized trial (N-MOmentum), inebilizumab was found to prolong the time to subsequent NMO relapse and reduce worsening of disability and radiological (MRI) measures of disease activity.”

“The results were even more significant, considering that no immunosuppressive agents were used in this trial as comparators or combined therapy,” they added.

Changing the Treatment Landscape 

Whenever new therapies are introduced that demonstrate superior efficacy and safety compared to existing drugs, healthcare professionals everywhere have reason to celebrate. In the case of NMOSD, this means that clinicians have more drugs at their disposal that are officially approved. Waliszewska-Prosół commented, “Instead of empirical or “off-label” use, there is an increasing trend for recommending officially approved therapies based on evidence from randomized controlled trials.”

Levy and colleagues also commented on what these new therapies could mean to NMOSD patient care. They wrote, “In countries where all three of these new treatments are approved for clinical use, clinicians are now faced with a changing landscape of options to offer their patients with NMOSD, who might have different priorities among efficacy, safety, cost, monitoring burden, and logistics.” 


Levy M, Fujihara K, Palace J. New therapies for neuromyelitis optica spectrum disorderLancet Neurol. 2021;20(1):60-67. doi:10.1016/S1474-4422(20)30392-6

Waliszewska-Prosół M, Chojdak-Łukasiewicz J, Budrewicz S, Pokryszko-Dragan A. Neuromyelitis optica spectrum disorder treatment-current and future prospectsInt J Mol Sci. Published online March 10, 2021. doi:10.3390/ijms22062801