Efficacy And Safety Of Tacrolimus Treatment For Neuromyelitis Optica Spectrum Disorders

Part 1 Evaluation of the efficacy and safety of tacrolimus treatment for neuromyelitis optica spectrum disordersOBJECTIVE:This clinical observation study attempts to:⑴understand the efficacy and safety of tacrolimus in the treatment of NMOSD;⑵analyze the factors that can predict relapse in tacrolimus treatment for NMOSD.Methodology:We retrospectively reviewed the NMOSD patients who were receiving or had received oral tacrolimus for more than 6 months to prevent relapse in Tongji hospital,Tongji Medical College,Huazhong University of Science and Technology（HUST）from Jan 1,2011 to Oct 1,2016.We collected the clinical data via electronic medical record systems.All the patients were diagnosed based on 2015 international consensus on NMOSD diagnostic criteria.Serum AQP4-IgG titers had been performed in all the patients included before treatment.Statistical analysis was performed in ARR,EDSS and relapse risk using IBM SPSS Statistics（version 20.0 for Windows;SPSS Inc.,Chicago,IL）.Mann-Whitney U test and the Fisher’s exact test were used for continuous variables and categorical ones,respectively.Wilcoxon signed rank tests were used to compare ARR and EDSS scores before and after treatment.The possibility of being free of relapses after treatment was compared between different titers of AQP-4 antibodies using log-rank test.Cox proportional hazards regression model was used to explore the relative risk of recurrence after tacrolimus treatment factor.P<0.05 was considered as statistical significance.Results:Twenty-five patients with NMOSD were included eventually.Tacrolimus treatment could reduce the annual relapse rate by 86.2%and significantly improved the EDSS score（4.5 vs 2.3;P<0.001）.Relapse was mainly related to the serum AQP4-IgG titer before treatment（P=0.028）.An univariate analysis via Cox proportional hazards regression model showed that patients with high serum AQP4-IgG titers（AQP4-IgG≥1:64）had high risks of relapse than those with lower ones（AQP4-IgG<1:64）(HR:5.665;CI₉₅:1.012-31.705;P=0.048),although no statistical significance was found between the two groups by adjusted multivariate analysis（P=0.061）.Conclusions:Tacrolimus can significantly reduce the relapse of patients with NMOSD and improve their neurological disabilities.Relapse after tacrolimus treatment may be associated to pretreatment serum AQP4-IgG titers,and serum AQP4-IgG titers may be an important factor in predicting relapse.Part 2 Comparison of the efficacy and safety between tacrolimus and azathioprine in the treatment of neuromyelitis optica spectrum disordersPURPOSE: This controlled clinical trial sought to understand the differences of the efficacy and safety between tacrolimus and azathioprine in the treatment of NMOSD.Methodology: We retrospectively reviewed the NMOSD patients who were receiving or had received oral azathioprine for more than 6 months to prevent relapse in Tongji hospital,Tongji Medical College,Huazhong University of Science and Technology（HUST）from Jan 1,2011 to Oct 1,2016.We collected the clinical data via electronic medical record systems.All the patients were diagnosed based on 2015 international consensus on NMOSD diagnostic criteria.Their relapse rate,EDSS score and adverse events were recorded and compared with the patients receiving tacrolimus to prevent relapse during the same period.The statistical software was used for statistical analysis using IBM SPSS Statistics.The continuous variables and categorical variables were Mann-Whitney U test and Fisher exact test respectively.Differences at P <0.05 were considered statistically significant.Results: Twenty-nine patients with NMOSD were included in azathioprine group.Azathioprine significantly reduced the ARR of patients with NMOSD by 77.8%（P<0.001）,but the EDSS score did not improve significantly,with a decrease of 9.3%（P=0.329）.The patients in the tacrolimus group were superior to those in the azathioprine group in terms of relapse-free rate and stabilized or improved EDSS scores（relapse-free rate: 72% vs 48%,P=0.1;stabilized or improved EDSS score rate: 96% vs 62%,P=0.003）.Two thirds of the relapses in the tacrolimus group occurred within the first 7 months,while only 39.1% of the relapses in the azathioprine group developed during the same period.Overall adverse events and serious adverse events were both higher in the azathioprine group than in the tacrolimus counterpart,although neither of the differences reached statistical significance（P=0.223;P=0.056）.Conclusions: Both tacrolimus and azathioprine can reduce the relapse of patients with NMOSD,but tacrolimus is superior to azathioprine in improving neurological dysfunction.Tacrolimus may be faster than azathioprine in taking in to effect.Also,tacrolimus may have some advantages in the incidence of side effects relative to azathioprine.