Efficacy and Safety of Zonisamide Addition in Children With Developmental Epileptic Encephalopathy/Epileptic
Peijiao Liu1,2,3,4,5, Li Zhang1,2,3,4, Qiao Zeng1,2,3,4
1Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Insights
Adjunctive zonisamide effectively reduces seizures in children with developmental epileptic encephalopathy (DEE/EE), showing sustained efficacy and good tolerability. This treatment is beneficial even for young children and those with highly drug-resistant epilepsy.
Area of Science:
- Pediatric Neurology
- Epileptology
- Pharmacology
Background:
- Developmental and Epileptic Encephalopathies (DEE/EE) represent severe forms of childhood epilepsy.
- Treatment of DEE/EE, particularly in young children and drug-resistant cases, remains a significant clinical challenge.
- Identifying effective and well-tolerated adjunctive therapies is crucial for improving outcomes.
Purpose of the Study:
- To assess the real-world effectiveness and safety of zonisamide as an add-on therapy for children diagnosed with DEE/EE.
- To specifically evaluate outcomes in younger children (under 6 years) and those with highly refractory epilepsy.
- To identify predictors of long-term treatment response.
Main Methods:
- An open-label, nonrandomized, self-controlled, real-world study was conducted.
- 127 children with DEE/EE were included, with data collected from 2020 to 2025.
- Primary endpoint was responder rate (≥50% seizure reduction) at multiple time points; secondary endpoints included seizure freedom, retention, and adverse events.
Main Results:
- Sustained responder rates of approximately 51-55% were observed throughout the 12-month study period.
- Seizure freedom was achieved in 23-27% of participants.
- Favorable efficacy was noted across different ages and etiologies, with female gender and fewer prior anti-seizure medications predicting better response.
Conclusions:
- Adjunctive zonisamide demonstrates sustained efficacy and a favorable safety profile in children with DEE/EE.
- The drug is effective in challenging populations, including young children and those with highly drug-resistant epilepsy.
- Zonisamide offers a reliable risk-benefit profile for managing refractory epilepsy in pediatric patients.
Objective:
To evaluate the real-world effectiveness and safety of adjunctive zonisamide in children with developmental epileptic encephalopathy/epileptic encephalopathy (DEE/EE), focusing on younger children and highly drug-resistant cases.
Methods:
This open-label, nonrandomized, self-controlled, real-world study included 127 children with DEE/EE at a single center from 2020 to 2025. The primary endpoint was the responder rate (≥ 50% seizure reduction) at 3, 6, 9, and 12 months, analyzed using last observation carried forward. Secondary endpoints included seizure freedom, retention, and adverse events (AEs). Multivariable analysis identified predictors of efficacy.
Results:
Responder rates were 51.2%, 55.3%, 53.7%, and 53.7% at 3, 6, 9, and 12 months, respectively. Seizure-free rates were 23.6%, 26.8%, 24.4%, and 27.6%. Efficacy was consistent across age and etiology. Female gender (OR = 3.00) and fewer prior anti-seizure medications (OR = 0.77) independently predicted 12-month response. Among children failing ≥ 5 prior medications, 44.3% responded, and 20.0% achieved seizure freedom. The 12-month retention rate was 81.9%. AEs occurred in 14.2%, most commonly reduced appetite (7.9%); most were tolerable.
Conclusion:
Adjunctive zonisamide provides sustained efficacy and favorable tolerability in children with DEE/EE, including young children < 6 years and highly drug-resistant cases. Gender and prior treatment history predict long-term efficacy, supporting its reliable risk-benefit profile for refractory epilepsy.
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