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[29]
firstly used in treatment acute leukemia and other Cree et al. firstly reported that RTX is refractory to
malignancies. The potent ability of suppressing the other immunosuppressive agents in an open labeled
development of some lymphocytes, especially B cells, trial of treatment of NMO. In this study, RTX was
2
guaranteed the therapeutic effect in treatment of some infused weekly at 375 mg/m for 4 weeks followed by
autoimmune diseases, such as aggressive relapsing MS. 1,000 mg reinfusion if CD19+ B cells were detectable
It was reported in 2006 among 5 patients with NMO. in the peripheral blood. Positive curative effect was
[24]
Although 2 patients experienced relapse during a observed in all cases with significant reduction of
2-year follow-up period, 4 of them benefited from the ARR (2.6 to 0) and EDSS (7.5 to 5.5). In another 5-year
[30]
treatment (12 mg/m monthly for 6 months and 3 cycles prospective study, Kim et al. reported that 26 of 30
2
at 3-month interval for maintenance) and 3 gained long- patients benefited from the treatment with a reduction
term remission. In another case, Kim et al. reported of ARR and stabilization of EDSS 18 patients totally
[25]
that 20 NMO patients infused with methotrexate (3-6 recovered in 24 months.
monthly cycles of 12 mg/m followed by 6-12 mg/m
2
2
maintenance doses) showed a reduction of ARR (2.8 to Dose-dependent strategies have been exploded in the
0.7) and EDSS (5.6 to 4.4). treatment of NMO. Generally, there are two different
regimens: one is discussed above in Cree’s study while
Methotrexate the other one is 1 g infusion at an interval of 2 weeks for
Methotrexate inhibits purine and thymidylate twice. The dose of RTX was adopted from the treatment
synthesis. A retrospective case of 14 NMO/NMOSD of B-cell malignancies which is considerably expensive
patients treated with methotrexate at a median dose and has a high probability of occurrence of side effects.
of 17.5 mg weekly showed a significant decrease of A Chinese group reported that repeated infusion with
ARR from 1.39 to 0.18. However, 13 out of 14 patients reduced dosage of RTX to five patients with NMO/
were co-treated with other immunosuppressive NMOSD was very effective in modulation of peripheral
[31]
agents: oralprednisolone (n = 11), rituximab (n = 1), B cells and prevention of relapse. The regimen was
or tacrolimus (n = 1), and the impact of these remains 100 mg per week for consecutive 3 weeks. One hundred
unknown. [26] milligram of RTX was reinfused when the percentage
of the B cells circulation reached 1%. None of the 5
Oral corticosteroids patients experienced relapse during the 1-year follow-
In addition to intravenous administration of up period. The median EDSS score slightly decreased
high dose for acute exacerbation, low dose of oral from 4.5 to 4, while all the patients got a significant
corticosteroids have been shown to be effective functional improvement after therapy. Despite the
in maintaining long-term remission. A cohort fact that this study indicated that responsiveness may
of 25 Japanese patients, receiving low-dose achieve in a lower dose in Asian patients, further
prednisolone (2.5-20.0 mg daily) as monotherapy investigations with a sufficient number of patients are
was retrospectively evaluated in a median period needed.
of 19.3 months. Results showed that ARR declined OTHERPROMISING THERAPIES
from 1.48 to 0.49. Meanwhile, this study indicated
the therapeutic effect was dose-dependent. Patients Complement-targeted therapy
receiving less than 10 mg/day were more susceptible As discussed above, complement activation pays an
to relapse. [27] important role in the pathogenesis of NMO. Eculizumab,
a humanized monoclonal anti-complement C5
Rituximab antibody, inhibits its cleavage by C5 convertase and
Rituximab (RTX) is a chimeric mouse/human subsequently blocks the complement cascade. In an
anti-CD20 monoclonal antibody that specifically open label clinical trial of 14 patients, intravenously
depletes peripheral CD20-positive B cells. This administration of 900 mg eculizumab every 2 weeks
antibody binds to the surface antigen on B cells significantly reduced ARR and improved the patients’
and activates complement-dependent cytotoxicity neurological deficits. Twelve of 14 patients got no
[32]
and antibody-dependent cell-mediated cytotoxicity. relapse after 12-month treatment, however one patient
It was firstly used in the treatment of lymphomas got meningococcal sepsis and sterile meningitis. In
and leukemia. Recently, RTX has been reported to be spite of this preliminary finding, the efficacy and
effective in treating certain autoimmune disorders safety of eculizumab should be further reviewed.
such as rheumatoid arthritis. RTX potently
[28]
suppresses autoimmune reaction by blocking the C5 is the key molecule of all the three complement
differentiation of B cells into plasma cells, antigen pathways. The infectious adverse effect above was
expression and release of cytokines simultaneously. likely due to the inhibition of the alternative and lectin

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