Factors influencing adverse reactions to adrenocorticotropic hormone treatment in infantile epileptic spasm syndrome: a single-center retrospective study

Background and Purpose Infantile Epileptic Spasm Syndrome (IESS) is a rare and severe developmental epileptic encephalopathy. Adrenocorticotropic hormone (ACTH) is regarded as one of the three major first-line treatment for IESS. However, the factors associated with the occurrence of adverse reactions during ACTH therapy remain unclear. This study aimed to identify and evaluate the clinical factors associated with the occurrence of adverse events (AEs) in patients with IESS undergoing ACTH therapy. Methods This retrospective case-control study included 94 patients with IESS who received ACTH therapy in Shanghai between March 2015 and November 2024. Cases were defined as those who developed clinical AEs. Propensity score matching was employed to minimize potential confounding factors. Association between potential risk factors and AEs were evaluated using the Mann-Whitney U tests and Spearman’s correlation analysis. Results Among the study cohort, 24 cases did not experience any AEs. Overall, patients with AEs were associated with a longer duration of ACTH treatment (13.34 vs. 11.79 days, p = 0.074) and a higher total cumulative dose (367.20 vs. 300.29 IU, p = 0.088). In subgroup analyses, respiratory system AEs showed no significant correlation with treatment duration or the cumulative dose. In contrast, the occurrence of hypertension was significantly associated with the daily average dose (25.53 vs. 1.81 IU/day, p = 0.021), the initial dose (22.12 vs. 9.29IU, p < 0.001) and initial average dose (2.73 vs. 1.21 IU/kg, p < 0.001) of ACTH. Conclusion Both the duration and cumulative dose of ACTH therapy are positively correlated with the incidence of AEs. The risk of hypertension during ACTH treatment for IESS is significantly linked to the initial dosing of ACTH. Careful consideration should be given to the selection of the initial ACTH dosage before initiating treatment for IESS.