Comparison Of Efficacy And Tolerability Of Three Immunotherapy Schemes For Neuromyelitis Optica Spectrum Disorder

Background:Neuromyelitis optica spectrum disorders(NMOSDs)is a group of central nervous system inflammatory demyelinating diseases mediated by humoral immunity,mainly involving the optic nerve and spinal cord.Aquaporin-4 immunoglobin G(AQP4-IgG)is its specific autoantibody.Most patients have a progressive or remission course of the disease.As the number of recurrences increases,the dysfunction of the patient continues to accumulate,which often leads to irreversible disabilities.Therefore,it is particularly important to prevent the recurrence of the disease.However,it is gratifying that in recent years many studies have shown that some immunosuppressive agents have a good effect on reducing the recurrence and the degree of disability of the patient.Azathioprine(AZA),Mycophenolate mofetil(MMF)and Rituximab(RTX)are the most commonly used immunosuppressive agents in our country.But the comparison of the efficacy and safety of the three has yet to be further studied.In previous studies,there are different rituximab regimens which have been widely used.According to Yang’s study,the lower dose of rituximab is sufficient to remove B cells and prevent disease progression in Chinese patients with NMOSDs.In addition,taking the high price of RTX and its possible side effects into account,we choose the lower dosage of RTX(100 mg RTX intravenous injection,once per week for 4 consecutive weeks)and compare it with AZA and MMF in the efficacy and tolerability.Objective:To observe and compare the efficacy and tolerability of azathioprine(AZA),mycophenolate mofetil(MMF)and lower dosages of rituximab(RTX)among patients with neuromyelitis optica spectrum disorder.Methods:In this prospective cohort,AQP4-IgG-seropositive patients with neuromyelitis optica spectrum disorder(NMOSDs)were enrolled and randomly divided into three groups,using AZA,MMF or lower dosages of RTX(defined as 100 mg RTX intravenous injection,once per week for 4 consecutive weeks)[1]respectively.Annualized relapse rate(ARR),EDSS scores,CD 19+ B-cell counts in peripheral blood,serum AQP-4-IgG titer and drug adverse reactions were compared between three groups.Results:In the AZA group(n = 22),MMF group(n = 30)and RTX group(n = 20),54.5%,60.0%and 65.0%of patients reached a relapse-free state and EDSS score improved in 90.9%,83.3%and 90.0%of patients respectively.In addition,there was significant reduction in ARR in all the three groups.Reduced dosage of RTX exerted a significant effect in reducing CD 19+ B-cell counts(P<0.01).Compared with the AZA group,the MMF group and the RTX group decreased the AQP-4-IgG titer evidently and caused fewer adverse events.Neither the Kaplan-Meier survival curves nor the Cox proportional hazard model indicated a significant difference in relapse among the three groups(P>0.05).Conclusions:AZA,MMF and reduced dosages of rituximab are all effective in reducing ARR and improving the clinical symptom of patients with NMOSDs.Lower dosages of RTX are more effective than the others in decreasing the CD 19 B-cell counts.MMF and reduced RTX decrease AQP-4-IgG titer more and cause fewer adverse events than AZA.However,more multi-center studies are still needed to find more effective therapeutic regimen.