Antiseizure Medications Show Similar Responses in Adult and Pediatric Patients

Jacqueline A. French, MD

Results from a meta-analysis of published studies containing data on antiseizure medications for adults suggest there is a comparable treatment response in children 2—12 years of age with primary generalized tonic-clonic seizures (PGTCS).

The baseline-subtracted median percent seizure reduction in seizure frequency ranged from 50.0% to 79.7% in children and 57.0% to 64.0% in adults across 7 adjunctive-therapy PGTCS trials.

In the topiramate group, children (n = 8; 4-16 years of age) had a responder rate of 50% while the adults in the topiramate group had a 58% responder rate, compared to 12% and 28% in the corresponding placebo groups, respectively. Additionally, researchers noted comparable rates of >50% reductions in seizure frequency in both lamotrigine and topiramate for the adjunctive therapy of PGTCS.

“This evidence, along with an understanding that PGTCS are similar in adult and pediatric patients with idiopathic (genetic) generalized epilepsies, supports the extrapolation of current labeling to pediatric patients for efficacy measurements,” senior author Jacqueline French, MD, professor of neurology, NYU Langone Health Comprehensive Epilepsy Center, and colleagues concluded.

Controlled trials in the treatment of PGTCS in adults and children 2—12 years of age published from 1970 to 2015 using predefined criteria were gathered from searches of EMBASE, Medline, and the Cochrane Central Register of Controlled Trials. In total, 7 published trials were eligible for the meta-analysis and investigators included all relevant data from the trials to eliminate any selective reporting or bias.

Of the 7 trials for the treatment of PGTCS, 4 assessed lamotrigine (n = 593), 1 perampanel (n = 81), and 2 topiramate (n = 80). In total, 2 trials were conducted with adults, 2 with adults and adolescents (12—16 years of age), 2 trials with adults and children, and 1 trial with adolescents and children.

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To compare drug efficacy in adults and children, researchers used median percent reduction in seizure frequency from baseline and >50% responder rates. Additionally, French and colleagues calculated standardized mean differences (SMD) between drug and placebo groups, standard error (SE) of those SMDs, odds ratios (ORs), risk ratios (RRs), and 95% confidence intervals (CIs) for each trial to determine relative strength of the baseline-subtracted efficacy measures in pediatric and adult populations. Researchers also used the Comprehensive Meta-Analysis V3.0 statistical analysis package for research synthesis.

French et al. noted that the confidence bounds across trials for >50% responder rates in seizure frequency were comparable between adults and children, and the estimated RRs and ORs “were consistently in favor of the drug group across trials and were very similar to the ≥50% responder rates seen in the adult population.” Additionally, evidenced by overlapping confidence intervals, the estimated risk ratios for each patient subgroup were comparable among the adult, adult plus children, and children subgroups in these studies.

“We did not find any substantial differences in the reported efficacy of the administered drugs between children and adults in 7 clinical trials, measured either by median percent reduction in seizure frequency from baseline or ≥50% responder rate,” the French and colleagues wrote.

REFERENCE

Nordli DR, Bagiella E, Arzimanoglou A, et al. Meta-analysis of drug efficacy in adult vs pediatric trials of patients with PGTC seizures. Neurology. 2020;94:1-8. doi: 10.1212/WNL.0000000000009325