The Analysis Of Efficacy,Safety Of MTOR Inhibitor Sirolimus For The Treatment Of Epilepsy In Pediatric Patients With Tuberous Sclerosis(TSC)

OBJECTIVE:To evaluate the overall efficacy of the mTOR inhibitor sirolimus in the treatment of tuberous sclerosis-associated epilepsy as a targeted therapeutic drug;further guidance by evaluating the patient's adverse effects during the follow-up period after taking the drug.Methods:(1)This study was a single-center,prospective,open-label clinical trial.The study type was a prospective cohort study;(2)by designing a case report form and completing the information entry through Epidata software,and completing the statistical analysis by SAS 9.4;(3)analyzing the mTOR inhibitor sirolimus in the treatment of tuberous sclerosis The effects of multiple complications;(4)to assess the safety of sirolimus in children with tuberous sclerosis.RESULTS:A total of 870 patients(483 males,387 females)who met the exclusion criteria were enrolled in the Children's Medical Center of the People's Liberation Army General Hospital.Among them,763 patients(360 males and 360 females)were followed up.The rate of loss of follow-up was 12.64%.The median age of all included patients was 1.2 years,and all enrolled patients completed more than 1 year of follow-up and completed relevant clinical examinations.1.The mTOR inhibitor sirolimus can effectively alleviate the seizure frequency of patients,and the effective degree is not related to the frequency of seizures in the first diagnosis.As of the last follow-up,46.00%of patients had complete remission of epilepsy,20.6%of patients had a control rate greater than 75%,3.9%had a control rate between 50%and 75%,and 29.5%had no significant relief of epilepsy.2,mTOR inhibitor sirolimus control of epilepsy in the long-term follow-up effect is better than short-term follow-up,24 months follow-up effect is better than 12 months,12 months follow-up effect is better than 6 months.After taking the drug,the proportion of epileptic seizures gradually increases with time.3,mTOR inhibitor sirolimus as a molecular targeted therapy,for the first diagnosis of patients with refractory epilepsy,the treatment effect is good,the total effective rate is 72.59%.4.Regardless of whether the patient changed the antiepileptic drug,the patient's epilepsy was effectively controlled during the 6 months,12 months,and 24 months of follow-up,and the mTOR inhibitor sirolimus was independent of the antiepileptic drug.5,mTOR inhibitor sirolimus is better than other forms of epilepsy in the control of infantile spasms,and all patients who completed 24 months of follow-up were effectively controlled.6.The mTOR inhibitor sirolimus can significantly reduce the E-chess score in patients with tuberous sclerosis,and the score decreases significantly with time.The mTOR inhibitor sirolimus was mainly controlled by epileptic seizures in patients with a reduced frequency of seizures,not because of a shortened course of disease(p=0.141),changes in anti epileptic drugs(p=0.005),and changes in seizure type(p?0.315).7,multiple linear regression results of patients with seizure frequency changes show that the control rate of epilepsy is mainly related to the patient's treatment age and epilepsy duration,the earlier the patient's treatment age,the shorter the course of disease,the higher the control rate of epilepsy.8.Safety evaluation of sirolimus:Sirolimus had no effect on patient height,weight,and BMI.At the same time,long-term follow-up did not reveal significant changes in blood routine,liver function,and renal function.38/763(5.8%)patients with oral ulcers,25/870(3.3%)patients with decreased appetite,37/870(5.0%)patients with mild liver function test results,17/870(2.5%)vomiting Patients,6/870(0.8%)patients with anemia.After symptomatic treatment,the above side effects can be cured,and no side effects of grade ? or above occur.Among all patients,there were no patients who died after taking the drug.Conclusion:This study established the largest single-center database of tuberous sclerosis in China and based on this analysis:mTOR inhibitor sirolimus can effectively treat tuberous sclerosis-related epilepsy,drug concentration is relatively safe,less adverse reactions It can be promoted in children with tuberous sclerosis.