A Meta-analysis On Efficacy And Safety Of Rituximab For Neuromyelitis Optica Spectrum Disorders

Objective: To assess the efficacy and safety of rituximab(RTX)in the treatment of neuromyelitis optic spectrum diseases(NMOSDs),and help guide clinical medication.Methods: The databases of Pubmed,Embase,Cochrane Library,CNKI,Wan fang were systematically searched by computer,and the search period was from the establishment of the databases until December 2020.To collect the trials of rituximab in the treatment of NMOSDs.The Cochrane risk-ofbias tool was used to assess the quality of the literature in the included Randomized controlled trial(RCTs).Newcastle-Ottawa Scale(NOS)was used to evaluate the quality of non-randomized controlled trial.Two researchers independently completed literature screening,quality assessment and data extraction.Statistical analysis was performed using Review Manager 5.3 and Stata 15.1 software to evaluate the efficacy of rituximab in NMOSD using a weighted mean difference and 95% confidence interval,and the size of test was set for 0.05.sensitivity analysis was performed on outcomes to verify the stability of the results of the meta-analysis.Results: There were 35 studies in the meta-analysis,including 5 RCTs and 30 observational studies with a total of 991 patients,of which 30 studies evaluated EDSS scores changes before and after rituximab treatment in patients with NMOSD and 24 studies evaluated the annualized relapse rate(ARR)changes before and after rituximab treatment in patients with NMOSD.4 studies assess ARR before and after treatment with rituximab versus azathioprine,and 3 studies assess EDSS scores before and after treatment with rituximab versus azathioprine in patients with NMOSD.3studies evaluated ARR and EDSS scores in NMO patients with AQP-4positive versus AQP-4 negative treated with rituximab.The literature included was middle quality in the study.Meta-analysis results revealed that NMOSDs patients treated with rituximab significantly reduced the ARR(WMD=1.46,95%CI : 1.24 ～ 1.68,P<0.01)and the EDSS scores(WMD=1.12,95%CI:0.97～1.28,P<0.01).rituximab is more effective than azathioprine in the treatment of NMOSDs(ARR:WMD=-0.54,95%CI:-0.75 ～-0.33;EDSS:WMD=-0.54,95%CI:-0.76 ～-0.32;P<0.0001).there was no difference in ARR and EDSS scores between AQP-4 positive and AQP-4 negative NMO patients treated with rituximab(ARR:WMD=-0.07,95%CI:-0.33～0.19,P=0.59>0.05;EDSS:WMD=-0.03,95%CI:-0.78～0.71,P=0.93>0.05).In this study,681 patients recorded safety data for RTX therapy,23%(156 patients)had adverse events(AEs),and 0.7%(5 patients)of NMOSDs discontinued due to severe adverse reactions.The major AEs including infusion reaction,upper respiratory tract infection,lower urinary tract infection and herpes zoster infection,they are mild to moderate,and are self-limited,rarely discontinue treatment.The sensitive analysis suggested that the results of meta-analysis were stable.Conclusions:NMOSDs patients treated with rituximab can significantly reduce the relapse frequency,increase EDSS scores,improve neurological dysfunction,and the efficacy is better than azathioprine.Rituximab has a high incidence of adverse reactions,but the disease is mild,and has a certain self-limited,medication should be cautious in clinical practice.