Efficacy Of Tacrolimus In The Treatment Of Refractory Myasthenia Gravis In The Short Term

Objective: To investigate the effect of different doses of tacrolimus(FK506)in the treatment of refractory myasthenia gravis(MG)in the short term,provided theoretical basis and data support for clinical treatment.Methods: 32 patients who were diagnosed with refractory myasthenia gravis in the Department of Neurology,Affiliated Hospital of Qingdao University from September 2015 to October 2017 were included in the study.Randomized digital tables were used to randomly classify the enrolled patients into two group,group A: tacrolimus 2 mg/d group,15 cases;group B: tacrolimus 3 mg/d group,17 cases.Compare the effect of tacrolimus at two,four,and twelve weeks in the two groups,and monitor the plasma concentration of tacrolimus at each observation time,as well as perform laboratory tests routinely,such as routine blood tests,fasting blood glucose,liver function and kidney function.At the same time,record the tacrolimus adverse reactions of patients.Results: Twenty-five of the 32 patients with MG completed the tacrolimus treatment for12 weeks in this trial,and a total of 7 fell out.Among them,4 patients in group A were exfoliated at 2 weeks after treatment because they did not reach the effective plasma concentration of 4-8 ng/ml;3 patients in group B were detached,1 patient could not afford tacrolimus and abandon the treatment,1 case was due to Severe diarrhea(6-7 times per day)withdrawal without continued use of tacrolimus.The MG patients who were eventually included in the study included 11 patients in group A and 14 patients in group B.Compared with pretreatment,there was no significant decrease in MG clinical score in group A patients who were treated with tacrolimus for 2 weeks,but the clinical scores of MG patients were significantly decreased at weeks 4 and 12,the results showed statistically significant(P<0.01);the clinical scores were all significantly decreased at the2 nd,4th,and 12 th weeks of tacrolimus treatment in group B,and there were significant differences(P<0.01).Within Group A,there was no significant decrease in the MG clinical score at the 2nd week of tacrolimus treatment compared with pretreatment,and statistical data support this result.The results of the comparison between the 4th week and the 2nd week were statistically significant,which was the same as the comparison result between the 12 th week and the 4th week(P<0.05);there was a significant difference between the above three groups in group B(P<0.05).Repeated-measures analysis of variance showed that there were differences in treatment outcomes between groups A and B(P < 0.05),and the treatment effects in groups A and B changed over time(P < 0.05),The results of the comparison between group A and group B showed that there was a statistically significant difference at the 2nd week and 4th week(P<0.05),but there was no statistically significant difference at the 12 th week(P>0.05).At the end of the trial,both group A and B showed effective treatment for tacrolimus,with a total effective rate of 81.25% and 83.33%,respectively.The blood concentration monitoring of all patients did not exceed the standard(>20 ng/ml).At 2 weeks of treatment,the plasma concentration of 4 patients in group A did not reach 4 ng/ml,and 1 patient exceeded the effective plasma concentration of 11.50 ng/ml;in group B,the plasma concentration of one patient in the group was 2.20ng/ml,and plasma concentrations of 3 patients were 12.6 ng/ml,13.89 ng/ml,and 16.80ng/ml;the plasma concentrations in the remaining treatment observation sites were 4-8ng/ml.The incidence of adverse reactions at the end of treatment was that in Group A,2patients presented with generalized pain,1 patient experienced joint pain and swelling;2patients in Group B had bloating and discomfort,and 1 had headache and nausea.All of these patients were given symptomatic treatment,then the symptoms disappeared.There were fewer total adverse events in the two groups at the end of treatment,and there was no significant difference between the two groups(p>0.05).Conclusions: Low-dose tacrolimus(2-3mg/d)in the short-term treatment of refractory myasthenia gravis patients can effectively improve myasthenic symptoms.Besides,tacrolimus is less likely to cause refractory adverse events and has higher safety.