A. Mahesan, S. Gulati, V. Sondhi, A. Agarwala, KL. Gupta, G. Kamila, P. Jauhari, B. Chakrabarty, et al. (2025). Safety, Efficacy, and Tolerability of Ketogenic Diet Versus Adrenocorticotropic Hormone in Infantile Epileptic Spasms Syndrome: A Randomized Controlled Trial. Pediatric neurology, 169, 196-203. https://doi.org/10.1016/j.pediatrneurol.2025.05.027

PubMed 40570615

[Abstract]
BACKGROUND: Ketogenic diet (KD) is efficacious in adrenocorticotrophic hormone (ACTH)-refractory infantile epileptic spasms syndrome (IESS) with lesser side effects. Upfront treatment with KD in IESS is least explored. This study aims to compare the efficacy of upfront treatment with KD compared with ACTH in IESS.

METHODS: In this open-label randomized controlled trial, infants aged 6-24 months with an electroclinical diagnosis of IESS were enrolled and randomly assigned to either the KD or the ACTH arm. The primary efficacy end point was to compare spasm reduction at six weeks of therapy from the baseline between the two arms. Secondary end points were electroclinical spasm cessation rates at six weeks, relapse after initial clinical response, adverse effects, and developmental progress at 24 weeks of follow-up.

RESULTS: A total of 178 children were screened; 87 children were randomized of which 41 received ACTH and 42 received KD. At six weeks of therapy, the median (interquartile range) percentage spasm reduction was comparable (66.7% [24.5-100] for ACTH vs 76.6% [56.3-100] for KD [P = 0.39]). The electroclinical spasm cessation rates were similar. There were higher relapses in the ACTH arm in those with initial clinical spasm cessation (38.9% ACTH vs 0 KD, P = 0.004) at 24 weeks' follow-up. The proportion of children having at least one side effect was higher in the ACTH arm (95.1% ACTH vs 59.5% KD; relative risk, 1.6 [1.23-2.1]).

CONCLUSIONS: KD may not be inferior to ACTH as first-line therapy for IESS with a better side effect profile and fewer relapses compared with ACTH.