Comparison Of The Safety And Effectiveness Between Intramuscular And Intravenous Administration Of ACTH For Infantile Spasms

Objective:This study evaluated the differences in safety and effectiveness between two administered routes(intramuscular vs.intravenous)of ACTH in treating infantile spasms for the short term.The factors affecting effectiveness and safety were also analyzed,which altogether can provide a reference and basis for optimizing the management of infantile spasms.Methods:Patients who were diagnosed with infantile spasms at the Shenzhen children’s hospital between March 1999 and October 2019 were enrolled.Inclusion criteria included the following four aspects.Clinical data within two months after initiating treatment of those patients who met both the inclusion and exclusion criteria were collected,including general clinical data(gender,routes of administration,onset age,lead time,comitant vitamin B6,neuroimaging findings,history of antiepileptic drugs,and the history of birth),the primary outcome measure of the study(adverse events occurred during treatment)and the secondary outcome measure of the study(spasms control outcomes).To improve comparability,we applied the propensity score matching method in this study to control confounding factors and reduce selection bias.Patients were matched at the ratio of 1:1 in the two groups(intramuscular vs.intravenous).After that,the effectiveness and safety were analyzed.Chi-square test,nonparametric rank-sum test,propensity score matching method,and binary Logistic regression analysis were applied in this study.SPSS 26.0 software was used for all of the statistical analysis.Results:A total of 237 patients were enrolled,adverse events happened in 95patients(40.1%)and cessation of spasms occurred in 77patients(32.5%).Of those 237 patients,129 in the intramuscular group(65.1% were female,median onset age was 5.0months old)and 108 in the intravenous group(59.3% were female,median onset age was5.0 months old).Before matching,there were statistically significant differences in general clinical data(comitant vitamin B6 and the history of antiepileptic drugs)between two groups(p<0.05).Propensity score matching yielded 86 patients in each group(172 patients in total),no significant differences were observed between the two groups with respect to general clinical data after matching(p>0.05).Spasm control outcomes were similar in both treatment groups(25.6% vs.36.0%,p=0.137),while adverse events were significantly lower in intramuscular group(19.8% vs.66.3%,p<0.01).No severe ACTH-related adverse events happened in either group.Univariate analysis showed a statistically significant difference in administration routes between patients who suffered adverse effects and those who did not(p<0.05).There were also statistically significant differences in onset age and history of antiepileptic drugs between patients who achieved cessation of spasms and those who did not(p<0.05).Multivariate Logistic regression analysis showed that administration route was an independent factor that affected the accident of side effects(intramuscular vs.intravenous OR=0.13,95%CI 0.06-0.26,p<0.01),the probability of side effects in the intramuscular group was lower than the intravenous group.Gender,onset age,lead time(the time between spasms onset and ACTH treatment),comitant vitamin B6,neuroimaging findings,history of antiepileptic drugs,and birth history did not independently affect the incidence of side effects.Onset age was an independent factor that affected the spasms control outcome(OR=2.34,95%CI 1.13-4.87,p=0.02),the probability of spasms cessation was higher in patients with older onset age(older than or equal to 5 months old)than those who onset earlier.The route of administration,gender,lead time,comitant vitamin B6,neuroimaging results,antiepileptic drug history,and birth history did not independently affect the spasms control outcomes.Conclusion: The short-term efficacy of two different administered routes(intramuscular vs.intramuscular)were similar in the treatment of infantile spasms.Intramuscular route protocol implied higher safety profile than intravenous route,and no severe ACTH-related adverse events occurred in either group.Children with infantile spasms who had failed more than two antiepileptic drug therapies were less likely to reach cessation of spasms through ACTH treatment.The probability of spasms cessation was higher in patients with older onset age(older than or equal to 5 months old)than those who onset earlier.