Researchers found no difference in efficacy between vigabatrin and adrenocorticotropic hormone (ACTH) for the second-line treatment of infantile epileptic spasms syndrome (IESS) after very high-dose prednisolone failed as a first-line treatment, according to a small, single-center retrospective study presented in November at the Child Neurology Society annual meeting.
Researchers analyzed data on 38 patients treated for IESS at Rady Children's Hospital between 2011 and 2024. Patients were between 1 and 24 months old at the time of IESS onset. Seventeen had been prescribed vigabatrin, and 21 ACTH.
Patients were excluded if the etiology of IESS was tuberous sclerosis, GLUT1 deficiency, or a known metabolic disorder. Follow-up ranged from 15 to 147 months (median 50 months).
The investigators found no difference between epileptic spasm control in the vigabatrin group and the ACTH group (29.4 percent vs. 19 percent, p=0.7029) or frequency of drug-resistant epilepsy later in life (p=1).
“After seeing three patients with IESS in clinic over the span of seven days, one of whom remitted after high-dose prednisolone and two of whom had recurrent spasms, I didn't find any good answers in the literature for what to do next, which led to the decision to conduct this retrospective review," said lead author Austin Layton, DO, a fifth-year resident in child neurology at the University of California, San Diego (UCSD) and Rady Children's Hospital. “While there are many good studies evaluating first-line therapy choices for IESS, we were unable to find a comparison of what to do when the first-line therapy fails."
At Rady Children's, Dr. Layton said, there is a slight preference for vigabatrin, but multiple patients still receive ACTH as second-line therapy for IESS refractory to high-dose prednisolone. “We talk a lot with families about pros and cons of both therapies," he said. “This analysis suggests that those conversations do not necessarily need to include an efficacy difference to say that one treatment is better than another. It helps us refocus the discussion around side effect profile."
Most conventional antiseizure medications are ineffective for IESS, noted E. Steve Roach, MD, FAAN, chief of the UT Health Austin Pediatric Neuroscience Program at Dell Children's Hospital, who was not part of the study. “These three core drugs are the only ones with evidence for their efficacy in this setting, and none of them work all the time. For years, there was an ongoing debate about whether ACTH or steroids should be first-line, but a series of clinical trials suggested that steroids are at least as effective as ACTH, and recent years have seen a trend toward prednisolone as first-line treatment."
There are pros and cons to both second-line therapies. Vigabatrin, which can only be prescribed under a risk evaluation and mitigation strategy program, has a black-box warning noting that it is associated with a risk of vision damage in 30 percent of patients as well as with electrolyte disturbances and MRI changes in the brain.
ACTH also is associated with electrolyte disturbances plus serious infections and arterial hypertension. ACTH and steroids can cause electrolyte disturbances as well as serious infections and arterial hypertension, Dr. Roach said. On the practical side, ACTH is far more costly and requires regular intramuscular injections, while vigabatrin is an oral agent.
But is there an efficacy difference? The UCSD review suggests there is not. “These findings are intriguing, although of course it is a retrospective analysis with a fairly small number of patients," Dr. Roach said. “It's probably not going to be the final answer to much of anything. But as a preliminary study it is quite useful and suggests the need for a more comprehensive trial. Assuming that the findings can be confirmed, if there is an oral medication that is less expensive and works just as well without the pain of intramuscular injections, this would be quite exciting."
Child Neurology Society Abstract GAT2-2: Layton A, Sattar S, Gold J, et al. Vigabatrin versus ACTH as second-line therapy after very high-dose prednisolone failure for the treatment of epileptic spasms.
https://journals.lww.com/neurotodayonline/blog/NeurologyTodayConferenceReportersCNSAnnualMeeting/pages/post.aspx?PostID=60
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