Neuromyelitis Optica Spectrum Disorder (NMOSD)

Interleukin 6 Receptor Blockers

Satralizumab (Enspryng™) and tocilizumab (Actemra®) are interleukin 6 (IL-6) receptor blockers that have demonstrated effectiveness in treating neuromyelitis optica spectrum disorder (NMOSD). 

Satralizumab is currently US Food and Drug Administration (FDA)-approved for the treatment of adult patients with NMOSD who have anti-aquaporin-4 (anti-AQP4) antibodies following the publication of 2 randomized placebo-controlled clinical trials. Studies comparing satralizumab to other immunosuppressants are currently underway.1 For example, a multicenter, single-arm, open-label study is aiming to evaluate its effectiveness as a monotherapy or in combination with azathioprine, mycophenolate mofetil, or corticosteroids.2 

Tocilizumab is not FDA-approved for the treatment of NMOSD; however, it appears to be more effective and well tolerated compared to azathioprine according to a phase 1/2 clinical trial.3 An open-label phase 3 trial is currently being conducted to determine the long-term safety and effectiveness of tocilizumab.4

The current role of IL-6 blockers as therapeutic agents for NMOSD are discussed in detail elsewhere. 

Read more about IL-6 pathway inhibitors


Benlysta® (belimumab) is the first FDA-approved targeted biological treatment for systemic lupus erythematosus patients with active, autoantibody-positive disease, and it was approved in 2011. It works by inhibiting a member of the tumor necrosis factor superfamily called B-lymphocyte stimulator (BLyS), also known as B-cell activating factor. BLyS interacts with receptors on B-cells to promote their survival and the function of activated autoreactive B-cells, and overexpression of BLyS is associated with decreased self-tolerance in murine models.5  An open-label trial is currently being conducted to determine the efficacy and safety of belimumab in adult patients with NMOSD. Researchers will measure, among other parameters, time to relapse, changes in Expanded Disability Status Scale (EDSS), and the number of new and/or enlarging T2 hyperintense lesions on magnetic resonance imaging from baseline to 52 weeks.6 


Ultomiris® (ravulizumab-cwvz), a modified form of eculizumab, is a long-acting complement inhibitor with a reduced affinity for complement component C5 at endosomal pH. This drug has been developed to address the dosing limitation associated with eculizumab, which must be administered intravenously at weekly intervals initially, then intravenously every 2 weeks. The modifications allow Ultomiris to bind C5 at physiologic pH but dissociate from it once inside the acidic environment of an endosome. The antibody detaches from C5 inside the endosome, evades lysosomal degradation, and is recycled. The increased half-life of ravulizumab allows less frequent dosing at once every 8 weeks. Currently, Ultomiris is not FDA-approved for the treatment of NMOSD. A phase 3, external placebo-controlled, open-label trial is underway, which aims to determine the efficacy of Ultomiris in AQP4-positive NMOSD patients (NCT04201262). The expected completion date is July 2024.7 


Imotopes™ are synthetic peptides encompassing human leukocyte antigen (HLA) class II epitopes flanked by a thioreductase motif that can bind HLA class II antigens and elicit a cytolytic response. A phase 0 study is currently being conducted to determine the binding of different Imotopes to different HLA class II antigens on mononuclear cells from the peripheral blood of patients with NMOSD. The purpose of the study is to identify specific HLA antigens present in each patient and to study the binding of the synthetic peptides to these targets. Ultimately, the goal of the study is to identify which peptides are capable of inducing a cytotoxic response after binding with their target antigens, which are directed towards immune cells involved in the maintenance and triggering of disease. The study is expected to be completed in February 2023.8


SHR1459 is a noncovalent, reversible Bruton tyrosine kinase (Btk) inhibitor. Btk is expressed in most cells of hematopoietic lineage, especially B-cells, mast cells, and macrophages, and it is not present in T-cells, NK cells, or plasma cells. Btk plays important roles in the development, maturation, and differentiation of immature B-cells and the overall survival of mature B-cells.9 An open-label, phase 2 clinical trial is being conducted in adult patients with NMOSD with AQP4-immunoglobulin G (IgG) antibodies. It aims to determine the efficacy and safety of SHR1459 as well as if the investigational agent prevents relapses of NMOSD. It is expected to conclude in September 2022.10 


CT103A is a novel, fully humanized B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) that has shown efficacy in the treatment of refractory/relapsed multiple myeloma. BCMA is expressed on the surface of plasma cells implicated in the pathogenesis of different antibody-mediated idiopathic inflammatory diseases of the nervous system such as NMOSD and myasthenia gravis. Researchers hypothesize that BCMA may be a viable target for treating these diseases and have developed CAR T-cells against BCMA in an attempt to eliminate abnormal plasma cells from the serum of these patients.11 An open-label clinical trial is currently being conducted to evaluate the efficacy and safety of CT103A cells in antibody-associated idiopathic inflammatory diseases of the nervous system, including NMOSD. For NMOSD, the investigators will measure any decrease in concentration of AQP4-IgG titers in the serum after infusion with CT103A cells over the course of 2 years. The expected completion date is December 2023.12 


1. Enspryng. Prescribing information. Genentech, Inc.; 2020. Accessed March 28, 2022.

2. A study to evaluate the safety and efficacy of satralizumab in participants with neuromyelitis optica spectrum disorder (NMOSD). December 9, 2020. Updated March 17, 2022. Accessed March 28, 2022.

3. Zhang C, Zhang M, Qiu W, et al; TANGO Study Investigators. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. 2020;19(5):391-401. doi:10.1016/S1474-4422(20)30070-3

4. An open label extension trial of eculizumab in relapsing NMO patients. December 6, 2013. Updated February 17, 2021. Accessed March 28, 2022.

5. Dubey AK, Handu SS, Dubey S, Sharma P, Sharma KK, Ahmed QM. Belimumab: first targeted biological treatment for systemic lupus erythematosus. J Pharmacol Pharmacother. 2011;2(4):317-319. doi:10.4103/0976-500X.85930

6. Efficacy and safety of belimumab in neuromyelitis optica spectrum disorders. December 13, 2021. Updated January 6, 2022. Accessed March 28, 2022. 

7. An efficacy and safety study of ravulizumab in adult participants with NMOSD. December 17, 2019. Updated February 21, 2022. Accessed March 28, 2022. 

8. In vitro study of the biological and immunological activity of Imotopes® candidates on blood cells of patients with stabilized NMO. November 16, 2020. Updated July 1, 2021. Accessed March 28, 2022.

9. Brullo C, Villa C, Tasso B, Russo E, Spallarossa A. Btk inhibitors: a medicinal chemistry and drug delivery perspective. Int J Mol Sci. 2021;22(14):7641. doi:10.3390/ijms22147641

10. An open label study of the effects of SHR1459 in NMOSDs patients. December 17, 2020. Updated October 20, 2021. Accessed March 28, 2022.

11. Wang D, Wang J, Hu G, et al. A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma. Blood. 2021;137(21):2890-2901. doi:10.1182/blood.2020008936

12. Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Idiopathic Inflammatory Diseases of the Nervous System (CARTinNS). September 23, 2020. Updated January 26, 2022. Accessed March 28, 2022.

Reviewed by Hasan Avcu, MD, on 3/28/2022.