Vigabatrin Plus Hormonal Therapy Superior in Infantile Spasms

The combination of vigabatrin and hormonal therapy was found to be significantly more effective in stopping infantile spasms than hormonal therapy alone, according to results from the International Collaborative Infantile Spasms Study (ICISS).¹

Infantile spasms is a frequently devastating epileptic encephalopathy that may lead to a regression in neurodevelopment^, and delays in treatment may lead to worse outcomes.¹ Adrenocorticotrophic hormone (ACTH) or prednisolone and vigabatrin are currently the preferred first-line therapeutic options.²

In a previous study,³ in which  researchers compared hormonal treatment with prednisolone or tetracosactide depot to vigabatrin for infantile spasms^, some children who did not initially respond to the first treatment responded quickly to the alternative treatment. In the current study,  the authors hypothesized “that combining hormonal and vigabatrin therapy would achieve spasm cessation in 4 weeks (between day 14 and 42 of treatment) in a greater proportion of infants than with hormonal therapy alone.”

ICISS included infants aged 2 to 14 months who had a clinical diagnosis of infantile spasms and findings of hypsarrhythmia on an EEG. Infants were randomized to receive either hormonal therapy with vigabatrin (n= 186) or hormonal therapy alone (n= 191). Prednisolone was administered as 4 10 mg doses/d, while tetracosactide depot was administered as 0.5 mg on alternate days. Vigabatrin was dispensed at 50 mg/kg/d for the first 2 doses and increased to 100 mg/kg/d after 24 hours. If spasms continued after 72 hours, the dosage was increased to 150 mg/kg/d.

The authors found that the cessation of spasms was higher for the combination group compared with the group that received hormonal therapy alone (72% vs 57%; 95% CI 5.1-24.9; P= .002). The outcome remained significant after controlling for the risk of developmental impairment, type of hormone treatment, and whether or not hormonal treatment was randomized (Odds Ration [OR]: 2.1, 95% CI 1.3-3.2; P= .001). Notably, infants who had a lead time to treatment greater than 2 months had a statistically significant decline in response rate (P= .0138).

“This multicenter study is the largest randomized trial on the treatment of infantile spasms to date and shows that a combination of hormonal therapy tetracosactide or high dose prednisolone) is more effective at stopping spasms between days 14 and 42 than hormonal therapy alone,” said Raili Riikonen, MD, PhD, a senior researcher at the University of Kuopio in Finland, who authored an editorial on the study.⁴ Noting that managing adverse effects and early diagnosis and treatment are keys to success, she pointed out that “future research will be needed to address several key questions: later developmental outcome, incidence of relapse rate, and next-line therapy for no-responders,” she told Neurology Advisor.

References

1. O’Callaghan FJ, Edwards SW, Alber FK, et al. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. Lancet Neurol. 2016 Nov 9; doi: 10.1016/S1474-4422(16)30294-0. [Epub ahead of print]
2. Iyer A, Appleton R. Improving outcomes in infantile spasms: role of pharmacotherapy. Paediatr Drugs. 2016;18:357-66.
3. Lux AL, Edwards SW, Hancock E, et al. The United Kingdom infantile spasms study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial. Lancet Neurol. 2005;4:712-7.
4. Riikonen R. Combination therapy for treatment of infantile spasms. Lancet Neurol. 2016 Nov 9; doi:10.1016/S1474-4422(16)30276-9. [Epub ahead of print]