Abstracts

Rationale: Infantile spasms (IS) are a serious infantile epileptic encephalopathy. The spasms occur in association with hypsarrhythmia or similar on EEG. There is often coincident psychomotor arrest or regression. We hypothesised that combination treatment of hormonal therapy plus vigabatrin would be associated with a greater proportion of infants achieving spasm cessation than would be the case with hormonal therapy alone and that combination therapy would also be associated with a better developmental outcome.Methods: Between March 2007 and May 2014, infants with IS and a compatible EEG were enrolled in a multicenter treatment trial. Participating countries were the UK, Germany, Switzerland, Australia and New Zealand. 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. Hormonal treatment was continued for 2 weeks and then weaned over 2 weeks. Vigabatrin was continued for 3 months and then weaned over a month. The early primary outcome measure was cessation of spasms on and between days 14 and 42. An electro-clinical response was defined as cessation of spasms on and between days 14 and 42 plus resolution of hypsarrhythmia on EEG. Analysis is by intention to treat.Results: 377 children were enrolled and early clinical outcome data is 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 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 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 was available in 374 infants. 123/85 (66.5%) on combination therapy versus 104/189 (55%) on hormonal therapy alone achieved an electro-clinical response: treatment difference 11.5% (95% CI 1.4% to 21.6%, p = 0.02).The treatment effect favouring combination therapy with respect to electro-clinical outcome remained highly significant in the multivariate logistic regression (Odds ratio 1.7 (95% CI 1.12 to 2.62) p = 0.013).Conclusions: Combination therapy of vigabatrin plus hormonal therapy is associated with a significantly superior early clinical and electro-clinical outcome.