Factors Influencing the Response of Infantile Epileptic Spasm Syndrome Patients to ACTH as Repeated First-Line Therapy
Authors: Ge Wenrong , Pang Ping , Zhang Ziyan , Wan Lin , Yang Guang 
Published: October 2024

Objective
The treatment of infantile epileptic spasm syndrome (IESS) aims to achieve spasm control. Current first-line interventions include hormonal therapy (adrenocorticotropic hormone [ACTH] and corticosteroids) and vigabatrin. Despite treatment, the response rate remains at around 40%, with some patients experiencing relapse after initial control. In certain cases, a second course of first-line therapy may be warranted. This study aims to perform a secondary analysis of data from previously published studies by our research group to elucidate factors influencing the efficacy of ACTH when re-administering it after first-line treatment failure.
Methods
We conducted a retrospective analysis of clinical data from children with IESS who had failed or relapsed following initial first-line therapy and subsequently received ACTH at our institution as a second-line treatment. We examined such variables as etiological classification, interval between treatments, age at first epileptic seizure, radiological findings, and changes in pharmacological treatment modalities to assess their impact on the short-term response to the second administration of first-line therapy.
Results
Among 128 IESS patients identified, 50 (39.1%) achieved a short-term response. Comparative analysis indicated that responders had a shorter duration since initial first-line therapy (median 1.00 [interquartile range, IQR 0.00, 2.00] vs. 1.75 [IQR 0.50, 3.88] months), were younger at the time of repeated treatment (median 11 [IQR 8, 17] vs. 16 [IQR 10, 24] months, p = 0.008), and were less likely to present with additional seizure types during spasm episodes (12.0% vs. 28.2%, p = 0.030). A multivariate logistic regression model, adjusted for selected variables, revealed that a higher age at the onset of the first epileptic seizure and prior response to first-line therapy were associated with increased odds of achieving a short-term response to subsequent ACTH treatment (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.39, 7.23, p = 0.014). Conversely, older age at the time of repeated first-line treatment, older age at the spasm onset, and an etiology of congenital structural anomalies without genetic aberrations were associated with lower odds of a short-term response (OR = 0.85, 95% CI = 0.78, 0.92, p < 0.001; OR = 0.43, 95% CI = 0.16, 0.82, p = 0.032; OR = 0.18, 95% CI = 0.04, 0.69, p = 0.016).
Conclusion
A subset of children with IESS may benefit from a second trial of ACTH therapy even after initial first-line treatment failure, with over one-third of patients achieving a short-term response. However, patients with congenital structural anomalies without genetic alterations may not be suitable candidates for further ACTH therapy. Additionally, an older age at the first epileptic seizure onset correlates with a higher likelihood of a short-term response, while a later age at spasm onset inversely affects the probability of response. Younger age at the time of ACTH re-treatment may also increase the chances of a short-term response. Consideration for ACTH therapy may be warranted in relapse cases after an initial short-term response to first-line treatment.