Levetiracetam increased time between seizures for infants with epilepsy

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Levetiracetam may be a superior initial treatment for infants with nonsyndromic epilepsy, a multicenter, prospective, observational study has shown.

“Our findings suggest that levetiracetam has superior effectiveness compared with phenobarbital as initial monotherapy for nonsyndromic epilepsy in infants,” wrote Zachary Grinspan, MD, director of the pediatric epilepsy program at Cornell University, New York, and his colleagues. “We estimate that for every 100 infants with epilepsy treated with levetiracetam instead of phenobarbital, 44 infants would be free from monotherapy failure instead of 16.”

To evaluate the effectiveness of levetiracetam vs. phenobarbital, Dr. Grinspan and his colleagues developed the Early Life Epilepsy Study, a multicenter, prospective, observational investigation of 155 children with nonsyndromic epilepsy. Patient information for this study was obtained from medical records and was collected from March 1, 2012, through April 30, 2015. All of the patients in the study were observed in the first 3 years of life.

Of the 155 children included in the analysis for this study, 117 were treated with levetiracetam and 38 with phenobarbital. There were some differences between the groups. Children treated with levetiracetam were, on average, 2 months older at seizure onset than were those in the phenobarbital group (5.2 months vs. 3.0 months; P less than .001). Infants treated with levetiracetam also tended to begin treatment further from the time of their first seizure and exhibited less developmental delay at the time of epilepsy diagnosis. There were some other differences of possible clinical importance (developmental structural brain abnormalities, head circumference) that did not reach statistical significance.

Freedom from monotherapy failure was greater in the levetiracetam group (47 [40.2%] vs. 6 [15.8%]; P = .01; odds ratio, 3.6; 95% confidence interval, 1.5-10). Overall, the researchers concluded that levetiracetam was superior to phenobarbital for nonsyndromic epilepsy in pediatric patients (OR, 4.2; 95% CI, 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]).

Outcome information was missing for more infants treated with levetiracetam than for those treated with phenobarbital, which could have skewed the analyses, Dr. Grinspan and his associates said. The nature of nonsyndromic epilepsy also makes it difficult to study because of the intricate genetic interactions that can influence the disorder.

Although this study provides information that could potentially benefit infantile epilepsy patients, the investigators said that more work must be done on the topic.

“A prospective clinical trial is needed. Levetiracetam and phenobarbital are both commonly used for infantile-onset epilepsy, indicating community equipoise regarding their relative effectiveness,” they wrote. “However, the effect size in our analysis was surprisingly large (number needed to treat, 3.5), suggesting that a change in practice could meaningfully improve outcomes.”

The investigators reported receiving grants and fees and consulting with a range of institutions, and the complete list can be found on the JAMA Pediatrics website. This study was funded by the Pediatric Epilepsy Research Foundation.

SOURCE: Grinspan Z et al. JAMA Pediatr. 2018 Feb 12. doi: 10.1001/jamapediatrics.2017.5211.

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