Effectiveness、Safety And Possible Influencing Factors Of Azathioprine Therapy In Neuromyelitis Optica Spectrum Disorder

Objective To evaluate the efficacy and safety of azathioprine(AZA)in the remission of neuromyelitis optica spectrum disorder(NMOSD),and to find factors that affect its efficacy and safety.Method Prospectively collected 54 patients with NMOSD in the First Affiliated Hospital of Guangxi Medical University from September 2015 to September 2018.Blood routine,liver function,renal function,cerebral + spinal MRI and visual function were regularly monitored after AZA treatment.Patients stable during follow-up and take AZA ≥6 months or patients with leukopenia were tested azathioprine metabolites(6-TGN,6-MMPN)concentration.Analyze the following: 1.Comparing the annual recurrence rate(ARR),extended disability scale(EDSS)score,and recording AZA-related adverse events before and after treatment,and evaluating their effectiveness and safety;2.Comparing ARR and EDSS scores between the autoantibodies positive and negative groups,un-derstanding the effects of positive autoantibodies on ARR,EDSS scores,and AZA efficacy;3.Comparing differences in ARR and EDSS scores between different serum AQP4-IgG concentrations,and understanding whether AQP4-IgG concentration affects annual recurrence of disease rate and disability damage,AQP4-IgG was reviewed half a year after AZA treatment,and the effect of AQP4-IgG outcome on disease activity was analyzed;4.Comparing differences in 6-TGN and 6-MMPN concentrations between patients with stable clinical symptoms and leukopenia,To assess whether 6-TGN and 6-MMPN concentrations can be used as indicators for predicting the efficacy of AZA.Result 1.54 patients with NMOSD received AZA(2.0-3.0mg/kg.d)treatment,the median time of treatment was 17.5(3-76)months,The median ARR decreased from 1.4(0.67-9.52)times/year before treatment to 0(0-2.38)times/year(P=0.000)after treatment,and 64.8%(35/54)had no clinical recurrence,median EDSS The score decreased from 3.0(1.0-8.5)points to 1.5(0-8.5)points(P=0.000).35.2%(19/54)patients had adverse drug events during follow-up,leukopenia was 22.2%,liver function abnormal was 9.3%,menstrual disorders was 5.6%,alopecia was 5.6%,infection was 3.7%;2.Autoantibody positive and negative patients,compared ARR,EDSS score,difference of ARR and EDSS score before and after treatment,there was no significant difference,P>0.05;3.There was no significant difference in ARR,EDSS score,difference of ARR and EDSS score among different serum AQP4-IgG titers,P>0.05;4.Compared with patients whose stable clinical condition,the 6-TGN concentra-tion of patients who leukopenia was higher,P=0.000.It’s suggest that higher 6-TGN concentration may be associated with leukopenia.Comparing 6-MMPN concentration,P=0.376,the difference was no significant,but the 6-MMPN of patients who leukopenia was higher than patients whose stable clinical condition.Conclusion AZA can significantly slow the recurrence of NMOSD and improve functional impairment of disabled patients,but some patients have adverse events such as leukopenia,liver enzymes abnormal,menstrual disorders,alopecia,infection;Positive autoantibody,different serum AQP4-IgG concentrations and AQP4-IgG outcome were no significant direct correlation between disease activity,cumulative degree of disability injury and the efficacy of AZA.Higher 6-TGN concentrations may be associated with myelosuppression.Monitoring 6-TGN and 6-MMPN concentrations may be used as indicators for predicting AZA efficacy.