Conference Coverage

Combo therapy outcomes for West syndrome prove no better than monotherapy



The current gold standard for treatment of West syndrome remains hormonal therapy with either adrenocorticotropic hormone (ACTH) or high-dose prednisone as monotherapy rather than in combination with vigabatrin, Hiroki Nariai, MD, declared at the International Epilepsy Congress.

Dr. Hiroki Nariai, pediatric neurologist at UCLA Bruce Jancin/MDedge News

Dr. Hiroki Nariai

West syndrome, or infantile spasms with a hypsarrhythmic EEG, is a severe infantile epileptic encephalopathy. It has high morbidity and mortality, and it’s challenging to treat. So neurologists and pediatricians were thrilled by an earlier preliminary report from an open-label, randomized, controlled trial conducted by the International Collaborative Infantile Spasms Study (ICISS) investigators. They reported that a hormonal therapy and vigabatrin (Sabril) combination provided significantly better seizure control between days 14 and 42 of treatment than hormonal therapy alone, albeit at the cost of more side effects (Lancet Neurol. 2017 Jan;16[1]:33-42).

However, a sobering update from the 377-infant study conducted in Australia, Switzerland, Germany, New Zealand, and the United Kingdom concluded that combination therapy didn’t result in improved developmental or epilepsy outcomes at 18 months, Dr. Nariai said at the congress sponsored by the International League Against Epilepsy.

“We still have inconclusive evidence to support the routine use of combination therapy. Clearly we need a better disease-modifying therapy because our best results with hormonal therapy or vigabatrin are only a 50%-70% response rate. And having a biomarker to guide early therapy and follow treatment response would help in establishing a better therapy,” commented Dr. Nariai, a pediatric neurologist at the University of California, Los Angeles.

He wasn’t involved in the international trial. He is, however, active in the search for a biomarker that would aid in speedier diagnosis of West syndrome, which in turn would allow for earlier treatment and, potentially, better outcomes. Indeed, Dr. Nariai has done pioneering work in identifying several EEG abnormalities readily measurable noninvasively using scalp electrodes that show considerable promise in this regard. These candidate biomarkers include ictal or interictal high-frequency oscillations at 80 Hz or more, along with cross-frequency coupling of high-frequency oscillations and delta-wave activity.

The primary endpoint in the ICISS study was developmental outcome at 18 months as evaluated using the Vineland Adaptive Behavior Scales composite score. The mean score was 73.9 in the combination therapy group and closely similar at 72.7 in the children on hormonal therapy alone. At 18 months, 30% of children in the combination therapy group carried a diagnosis of epilepsy, as did 29.2% of controls randomized to either high-dose oral steroids or intramuscular depot tetracosactide. About 15% of children randomized to combination therapy still had spasms at 18 months, as did 15.7% on hormonal therapy alone (Lancet Child Adolesc Health. 2018 Oct;2[10]:715-25).

The chief side effects of hormonal therapy included hypertension, hypoglycemia, and immunosuppression. Vigabatrin’s side effects included dose- and duration-dependent peripheral vision loss, movement disorders, and undesirable MRI signal changes.

Dr. Nariai observed that, even though hormonal therapy is widely used as first-line therapy in West syndrome, it remains surrounded by important unanswered questions.

“We don’t have head-to-head comparative studies of ACTH versus high-dose steroids, the optimal dosing protocol is not established, and we really don’t even know the mechanism of action for hormonal therapy and vigabatrin,” he said.

The study was sponsored by the U.K. National Institute of Health Research and other noncommercial entities. Dr. Nariai reported having no financial conflicts regarding his presentation.

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