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

BACKGROUND: Infantile spasms is a severe infantile seizure disorder that is difficult to treat and has a high morbidity. Absence of spasms on days 13 and 14 after randomisation is more common in infants allocated hormone treatments than in those allocated vigabatrin. We sought to assess whether early control of spasms is associated with improved developmental or epilepsy outcomes.

METHODS: Infants enrolled in the United Kingdom Infantile Spasms Study (UKISS) were randomly assigned hormone treatment (n=55) or vigabatrin (n=52) and were followed up until clinical assessment at 12-14 months of age. We assessed neurodevelopment with the Vineland adaptive behaviour scales (VABS) at 14 months of age on an intention to treat basis.

FINDINGS: Of 107 infants enrolled, five died and 101 survivors reached both follow-up assessments. Absence of spasms at final clinical assessment (hormone 41/55 [75%] vs vigabatrin 39/51 [76%]) was similar in each treatment group (difference 1.9%, 95% CI -18.3% to 14.4%; chi(2)=0.05; p=0.82). Mean VABS score did not differ significantly (hormone 78.6 [SD 16.8] vs vigabatrin 77.5 [SD 12.7]; difference 1.0, 95% CI -4.9 to 7.0; t(99)=0.35, p=0.73). In infants with no identified underlying aetiology, the mean VABS score was higher in those allocated hormone treatment than in those allocated vigabatrin (88.2 [17.3] vs 78.9 [14.3]; difference 9.3, 95% CI 1.2 to 17.3; t(95)=2.28, p=0.025).

INTERPRETATION: Hormone treatment controls spasms better than does vigabatrin initially, but not at 12-14 months of age. Better initial control of spasms by hormone treatment in those with no identified underlying aetiology may lead to improved developmental outcome.