## 7 Treatment Methods
### Immunosuppressive Treatment Methods  
Several drugs have been used in treating NMOSD, including immunosuppressant drugs such as glucocorticoidoids and azathioprine (AZA) and B cell-depleting drugs such as rituximab (RTX), mycophenolate mofetil (MMF), methotrexate, cyclosporine A, tacrolimus, mitoxantrone (MTX), IL-6 signalling blocking agents (tocilizumab and satralizumab), B cell inactivating agents (ocrelizumab and ilebilizumab), and complement pathway blocking drugs (eculizumab and IVIgs) [9,199]. A randomized clinical phase 2 trial was conducted among 118 NMOSD patients with anti-IL-6 receptor antibodies tocilizumab (TCZ) and AZA. The results revealed that TCZ was effective and safe compared to AZA in preventing relapses [200]. B cells are involved in NMOSD pathogenesis. B cells and CD19, CD23, and CD38 may increase peripheral blood circulation and reduce disease relapse in NMOSD patients [121]. AZA, a purine analogue, could effectively reduce relapse and restore neurological functions in NMOSD patients by inhibiting B and T cell proliferation and the induction of anti-inflammatory actions. AZA could be used along with corticosteroids for better results [201]. RTX is a monoclonal antibody that targets CD20 by displaying pre, mature, and memory B cells, resulting in the depletion of CD20\({}^{+}\) B cells and a reduction in pathogenic antibody production [199]. MMF improves clinical symptoms and suppresses disease activities and relapse. MMF inhibits monophosphate dehydrogenase, which involves guanosine nucleotide synthesis, and suppresses T and B cell synthesis and proliferation. MMF is an effective therapy compared to RTX and AZA, but has limitations such as teratogenicity and malignancy risk that need more clarification. Viral and bacterial infections are the side effects of MMF therapy [9]. MMF is more specific in targeting guanosine than AZA. The production and incorporation of thioguanosine into DNA results in treatment-induced lymphoma, as was reported in some AZA-treated cases. Thus, MMF is safe and efficient compared to AZA [202]. After three years of treatment with AZA, RTX, and MMF treatments, NMOSD patients revealed that RTX was more effective than MMF. AZA and RTX showed similar effects in reducing relapses and antibody levels [199]. Another potent immunosuppressive drug, MTX, acts as a DNA intercalating agent and causes structural disruption of DNA. It also negatively modulates DNA repair by inhibiting the repair enzyme topoisomerase II. MTX inhibits the proliferation of lymphocytes and macrophages [203; 204; 205]. Methotrexate is another common drug used for NMOSD and can be prescribed to long-term immunosuppressive patients. Methotrexate reduces acute relapses and is considered a safe drug for long-term usage. It suppresses the immune response in AQP4-IgG-seropositive patients by inhibiting dihydrofolate reductase (DHFR), which is critical in synthesizing nucleic acid precursors and causes T cell apoptosis [206; 207]. One more pathological feature of NMOSD is the terminal deposits of complement factors as lesions. This can result in CNS inflammation and astrocyte damage. Ecuilizumab treatment significantly reduced the number of relapses in NMOSD patients [208]. However, ecolizumab treatment promotes meningococcal and upper respiratory tract infections and pulmonary empyema [208]. The report says that the humanized monoclonal antibody satralizumab targets the IL-6 receptor but does not reduce pain and fatigue in NMOSD patients [209]. Satalizumab treatment in seropositive and seronegative AQP4 patients showed that it was ineffective in AQP4 seronegative patients [210]. and potentially active in seropositive patients [210]. Other drugs, including inebilizumab and ocelizumab, were also used to treat NMOSD. Several studies reported that antibodies targeting B cell and IL-6 receptors (such as RTX, inebilizumab, ocelizumab, tocilizumab, and satralizumab) and the complement inhibitor (Eculizumab) diminish the progress of the disease [211].