Combination of hormone therapy With Vigabatrin reduces Infantile Spasms better than hormone therapy alone

Results from the ICISS trial presented at the 69th Annual Meeting of the American Epilepsy Society (AES) suggest that a combination of hormonal therapy with vigabatrin reduces infantile spasms better than hormonal treatment alone. For this study, the ICISS trial researchers tested the hypothesis that combining prednisolone or tetracosactide with vigabatrin would result in a greater proportion of infants achieving spasm cessation compared with hormonal therapy alone.

Between March 2007 and May 2014, infants with IS and a compatible EEG were enrolled in a multicenter treatment trial. Infants were randomized to receive either hormonal therapy and vigabatrin or hormonal therapy alone. A second stage randomization allowed hormonal treatment to be allocated as either prednisolone or tetracosactide depot. Minimum doses were: vigabatrin 100 mg/kg/day, prednisolone 40 mg per day, or IM tetracosactide depot 0.5 mg on alternate days. The early primary outcome measure was cessation of spasms on and between days 14 and 42. Analysis was by intention to treat.

377 children were enrolled and early clinical outcome data will be available on 376 (1 case withdrew). 185 were allocated hormonal therapy and vigabatrin and 191 were allocated hormonal therapy alone. 133/185 (71.9%) on combination therapy versus 108/191 (56.6%) on hormonal therapy alone achieved a primary clinical response: treatment difference 15.3% (95% CI 5.4% to 25.2%, p=0.002). The treatment effect favouring combination therapy remained highly significant in a logistic regression analysis controlling for underlying aetiology, country of enrollment, whether hormonal therapy was randomized or not, and gender (Odds ratio 2.03, 95% CI 1.3 to 3.2, p=0.002). Treatment response was also significantly faster on combination therapy (median response time = 2 days, IQR 2–4 days) than hormonal therapy alone (median response time = 4 days, IQR 3–6 days, p<0.001).

The electro-clinical response, defined as cessation of spasms on and between days 14 and 42, in addition to resolution of hypsarrhythmia on electroencephalogram (EEG), as available for 374 infants showed that 123 of 185 (66.5%) on combination therapy versus 104 of 189 (55%) on hormonal therapy alone achieved an electro-clinical response, for a treatment difference of 11.5% (P = .02). The greater electro-clinical response in the combination therapy was also highly significant after multivariate logistic regression (OR, 1.7; P = .013).

The improved clinical and electro-clinical response to combined therapy was most marked in those children at lower risk of developmental delay at readmission.

Source: The International Collaborative Infantile Spasms Study (ICISS): Comparing Hormonal Therapies (Prednisolone or Tetracosactide Depot) and Vigabatrin Versus Hormonal Therapies Alone in the Treatment of Infantile Spasms: Early Clinical and Electro-Clinical Outcome. Abstract 2.255, AES 2015

Cover image credit: Hypsarrhythmia. Sorge and Sorge Italian Journal of Pediatrics 2010 36:36