Real-World Efficacy and Tolerability of Switching from Oxcarbazepine to Eslicarbazepine Therapy in Children Aged 6 Years or Older with Focal Epilepsy

Sooyoung Lyu; Juhyun Kong; Sang Ook Nam; Taek Jin Lim; Young Mi Kim; Gyu Min Yeon; Yun-Jin Lee

doi:10.26815/acn.2025.00850

Ann Child Neurol > Volume 33(3); 2025 > Article

Lyu, Kong, Nam, Lim, Kim, Yeon, and Lee: Real-World Efficacy and Tolerability of Switching from Oxcarbazepine to Eslicarbazepine Therapy in Children Aged 6 Years or Older with Focal Epilepsy

Original article

Annals of Child Neurology 2025;33(3):93-101.

Published online: June 25, 2025

DOI: https://doi.org/10.26815/acn.2025.00850

Real-World Efficacy and Tolerability of Switching from Oxcarbazepine to Eslicarbazepine Therapy in Children Aged 6 Years or Older with Focal Epilepsy

Sooyoung Lyu, MD^1,²

, Juhyun Kong, MD^1,², Sang Ook Nam, PhD^1,², Taek Jin Lim, MD^1,², Young Mi Kim, PhD³, Gyu Min Yeon, PhD⁴, Yun-Jin Lee, PhD^1,²

¹Department of Pediatrics, Pusan National University Children’s Hospital, Pusan National University School of Medicine, Yangsan, Korea

²Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea

³Department of Pediatrics, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea

⁴Department of Pediatrics, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea

Corresponding author: Yun-Jin Lee, PhD Department of Pediatrics, Pusan National University Children’s Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea
Tel: +82-55-360-2180, Fax: +82-55-360-2181 E-mail: jinnyeye@naver.com

Received March 10, 2025 Revised May 11, 2025 Accepted May 16, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

This study investigated the influence of prior use of oxcarbazepine (OXC) and other anti-seizure medications (ASMs) on seizure outcomes and tolerability when switching from OXC to eslicarbazepine acetate (ESL) or when adding adjunctive ESL therapy. Additionally, we aimed to evaluate other prognostic factors associated with ESL therapy in pediatric focal epilepsy.

Methods

ESL adjunctive or switching therapy was initiated in children aged ≥6 years with focal epilepsy. Patients were classified into those who received baseline ASMs including OXC (OXC-P group, switching from OXC) and those who received other ASMs excluding OXC (OXC-N group, adjunctive therapy). Reduction in seizure frequency and adverse events (AEs) were evaluated during follow-up.

Results

Seventy-two patients (mean age, 10.9±5.2 years) were included. The mean duration of ESL therapy was 6.1±3.7 months, and the mean maintenance dose was 16.3±5.6 mg/kg/day. The proportion of responders (≥50% reduction in seizure frequency) was 40.3% (29/72), without a significant difference between the OXC-P and OXC-N groups (17/50 [34.0%] vs. 12/22 [54.5%], P=0.169). Moreover, no significant between-group differences were noted in overall AEs (30.0% vs. 27.3%, P=0.981) or the retention rate (82.0% vs. 77.3%, P=0.886). Significant factors associated with a favorable response to ESL treatment were a higher ESL dose, shorter epilepsy duration, and fewer concomitant ASMs.

Conclusion

Switching from OXC to ESL or using adjunctive ESL therapy was effective and well-tolerated in children aged ≥6 years with focal epilepsy, irrespective of prior use of OXC in the baseline ASM regimen before initiating ESL therapy.

Keywords: Anticonvulsants; Oxcarbazepine; Eslicarbazepine; Child; Epilepsy

Introduction

Eslicarbazepine acetate (ESL), an anti-seizure medication (ASM) first introduced in 1999, received approval from the European Medicines Agency in 2009 and from the Food and Drug Administration (FDA) in 2013 as an adjunctive treatment for adults with focal seizures with or without secondary generalization. Subsequently, ESL was approved by the FDA as an adjunctive treatment for children aged >6 years and, more recently, for those aged >4 years with focal seizures [1]. In South Korea, ESL was approved in 2021 as an adjunctive therapy for adults and children aged ≥6 years with focal seizures.

ESL belongs to the dibenzazepine family, which also includes carbamazepine (CBZ) and oxcarbazepine (OXC); however, ESL has distinct structural differences [2]. These molecular variations result in different metabolites, rendering ESL less neurotoxic compared to CBZ and OXC [2]. The dibenzazepine family medications act as competitive blockers of voltage-gated sodium channels (VGSCs) [3]; however, the specific mechanisms of action differ among these medications. For example, CBZ primarily acts through fast inactivation of VGSCs, whereas ESL exerts its anticonvulsant effect by selectively enhancing slow inactivation of VGSCs, without significantly involving fast inactivation [4]. Such pharmacological differences suggest that both the combination of ESL with other dibenzazepines and the conversion from other dibenzazepines (such as CBZ and OXC) to ESL therapy might be feasible and could potentially lead to changes in seizure frequency [5].

Recent studies have evaluated the efficacy and tolerability of ESL as adjunctive therapy. Notably, several randomized controlled trials demonstrated the efficacy and tolerability of ESL as adjunctive therapy in adults [6,7], findings that have been corroborated by clinical practice experiences [3,5,8,9]. A previous report indicated that switching from CBZ to ESL in patients aged 16 to 70 years with treatment-resistant focal seizures did not significantly increase the risk of study discontinuation due to worsening seizure control or a higher frequency of side effects [5]. Other studies demonstrated that adjunctive ESL therapy improved seizure control and was generally well-tolerated in adult patients with focal epilepsy [3,6,8,9]. However, few prospective studies, systematic reviews, and meta-analyses have been conducted in children and adolescents [1,10-15]. In these studies, ESL was generally effective in reducing seizure frequency and was well-tolerated. A real-life retrospective study supported the long-term effectiveness and tolerability of ESL in children with predominantly drug-resistant epilepsy, based on data from three Canadian centers after approval (Table 1) [16]. Nevertheless, no real-world retrospective studies have specifically examined the effectiveness of switching from CBZ/OXC to ESL or adjunctive ESL therapy in pediatric populations. Among the dibenzazepine family medications, OXC is more commonly prescribed than CBZ for children with focal epilepsy at our pediatric epilepsy center.

The present study aimed to report our experience regarding the efficacy and tolerability of switching from OXC to ESL or using adjunctive ESL therapy in pediatric patients aged ≥6 years with focal epilepsy at a single tertiary center. Additionally, we aimed to investigate potential risk factors influencing ESL treatment outcomes. To the best of our knowledge, this is the first real-world retrospective study evaluating the effectiveness of switching from OXC to ESL or employing adjunctive ESL therapy in pediatric epilepsy.

Materials and Methods

1. Patients

This retrospective cohort study involved reviewing electronic medical records of patients treated with adjunctive ESL therapy for focal epilepsy at Pusan National University Children’s Hospital from September 2022 to March 2024. Inclusion criteria were as follows: (1) age 6 to 19 years; (2) diagnosis of focal seizure or focal to bilateral tonic-clonic seizure; (3) experiencing at least one seizure per month during the 6 months preceding ESL administration; (4) taking more than one ASM at baseline before initiating ESL, with no changes made to the ASMs during the study period except for OXC and ESL; and (5) receiving ESL maintenance therapy for at least 6 months. Patients with progressive neurological disorders or insufficient medical records were excluded. Patients were divided into two groups based on whether they received OXC at baseline: (1) the OXC-P group consisted of patients whose ASM regimen at baseline included OXC prior to starting ESL, who then switched from OXC to ESL (with no other sodium channel blockers included), and (2) the OXC-N group comprised patients receiving ASMs other than OXC.

2. Data collection and evaluation for outcomes of ESL treatment

The following data were collected: sex, seizure type, presence of intellectual disability, etiology of epilepsy, presence of a specific epilepsy syndrome, history of ketogenic diet/vagus nerve stimulation/epilepsy surgery, age at seizure onset, age at initiation of ESL therapy, duration of epilepsy, duration of ESL treatment, initial daily dose and maintenance dose of ESL (mg/kg/day), monthly seizure frequency, number of concomitant ASMs, reduction in seizure frequency, retention rate at the end of the study, and adverse events (AEs). Seizure semiology was categorized into dyscognitive only, focal motor and/or somatosensory, and focal to bilateral tonic-clonic seizures. Epilepsy etiology was classified as genetic/metabolic, infectious, structural, or unknown according to the 2022 International League Against Epilepsy classification of seizures and epilepsy. In the OXC-P group, patients switched from OXC to ESL (switching therapy), and the initial ESL dose was individualized, typically set at an OXC to ESL dose ratio ranging from 1:0.7 to 1:1. In the OXC-N group, ESL was initiated as adjunctive therapy at initial doses ranging from 7.5 to 10.1 mg/kg/day. In both groups, the optimal ESL maintenance dose was determined individually, based on clinical response and tolerability.

The response to ESL treatment was assessed by comparing mean monthly seizure frequency during a follow-up period of at least 6 months with baseline seizure frequency. Responses were categorized into seizure-free (100% reduction), 50%-99% reduction, 1%-49% reduction, or no change. A good response was defined as a seizure frequency reduction of ≥50% (seizure-free or 50%−99% reduction). Patients exhibiting a good response were classified as ‘responders,’ whereas those with a seizure frequency reduction of <50% were considered ‘poor responders.’ Changes in seizure frequency compared to baseline, AEs, retention rates, and reasons for discontinuation were recorded at each follow-up visit.

3. Statistics

All statistical analyses were performed using R software version 3.2.1 (meta package; R Foundation for Statistical Computing, Beijing, China), with two-sided statistical tests. Odds ratios with 95% confidence intervals were calculated to evaluate the effect of ASMs on all dichotomous outcomes and to examine differences between groups. Potential heterogeneity was assessed using the Q statistic, the chi-square test, and I². A random-effects model was applied to pool effect sizes if significant heterogeneity was detected (P<0.05 or I²>50%); otherwise, a fixed-effects model was used. Factors independently associated with a good response to ESL treatment were identified through multivariable logistic regression analysis. Statistical significance was set at P<0.05 for all analyses.

4. Standard protocol approvals and patient consent

Ethical approval for this study was granted by the Institutional Review Board of Pusan National University Yangsan Hospital (number: 05-2023-038). Written informed consent by the patients was waived due to a retrospective nature of our study.

Results

1. Demographic and clinical profile of the patients

This study included 72 children and adolescents (45 males and 27 females), aged 6 to18 years (mean, 10.9±5.2) at the initiation of ESL therapy. Table 2 presents the demographic and clinical characteristics of the OXC-P (n=50) and OXC-N (n=22) groups at ESL initiation. No significant differences were found between the OXC-P and OXC-N groups regarding sex ratio (male ratio, 58.0% vs. 72.7%, P=0.355), seizure type, etiologies, history of ketogenic diet (2.0% vs. 4.5%, P=0.965), mean age at seizure onset (6.6±3.6 years vs. 7.3±4.8 years, P=0.437), duration of epilepsy (3.2±1.5 years vs. 3.1±1.3 years, P=0.728), monthly seizure frequency at baseline (14.6±27.7 vs. 16.6±13.8, P=0.681), mean age at ESL initiation (10.7±4.7 years vs. 11.4±5.9 years, P=0.527), duration of ESL therapy (6.0±3.3 months vs. 6.3±2.9 months, P=0.294), ESL maintenance dose (15.7±5.5 mg/kg/day vs. 17.6±5.8 mg/kg/day, P=0.140), number of concomitant ASMs (2.1±1.4 vs. 2.2±0.9, P=0.556), or retention rate (82.0% vs. 77.3%, P=0.886) (Table 2).

2. Efficacy

Of the 72 patients, the proportions who became seizure-free (100% reduction), experienced a 50% to 99% reduction in seizure frequency, and qualified as responders (≥50% reduction in seizures) were 9.7% (7/72), 30.6% (22/72), and 40.3% (29/72), respectively (Fig. 1). Although the responder rate was slightly higher in the OXC-N group than in the OXC-P group (11/22 [50.5%] vs. 18/50 [36.0%]), this difference was not statistically significant (P=0.214) (Fig. 1).

Table 3 presents the comparison of demographic and outcome data between responders (n=29) and poor responders (n=43). No significant differences were noted between these two groups regarding sex ratio (male ratio, 62.1% vs. 62.8%, P=0.971), seizure type, etiologies, mean age at seizure onset (7.3±3.0 years vs. 6.5±3.1 years, P=0.277), seizure frequency (9.7±16.3 vs. 18.9±27.7, P=0.085), mean age at ESL initiation (10.7±3.8 years vs. 11.0±3.7 years, P=0.776), or proportion of patients in the OXC-P group (58.6% vs. 76.7%, P=0.169). However, responders had a significantly shorter mean epilepsy duration (2.5±1.4 years vs. 3.6±1.7 years, P=0.002), significantly higher ESL maintenance doses (18.5±6.5 mg/kg/day vs. 14.8±4.5 mg/kg/day, P=0.001), and notably fewer concomitant ASMs (1.5±0.8 vs. 2.5±1.4, P=0.001). Additionally, among 11 patients classified as having Lennox-Gastaut syndrome, six were responders, with five achieving freedom from seizures.

Multivariable logistic regression analysis identified independent factors significantly associated with seizure outcomes during ESL adjunctive therapy (Table 4). A good response (≥50% seizure frequency reduction) was positively correlated with higher ESL maintenance dose (P=0.004) and negatively correlated with longer epilepsy duration (P=0.014) and a greater number of concomitant ASMs (P=0.034).

3. Safety and tolerability

At least one AE was reported by 21 patients (29.2%), with some patients experiencing multiple events simultaneously (Table 5). The mean ESL dosage at the onset of AEs was 12.7±10.2 mg/kg/day. Somnolence was the most frequently reported AE (9/72, 12.5%), followed by headache (9.7%), dizziness (8.3%), nausea (6.9%), fatigue (5.6%), anxiety (2.8%), and insomnia (1.4%). No significant differences were observed between the OXC-P and OXC-N groups regarding the overall incidence of AEs, ESL dosage at AE onset, or types of AEs reported (Table 5). No severe or life-threatening AEs were recorded. All reported AEs were manageable and resolved over time through dose reduction or discontinuation of ESL. There were no significant laboratory abnormalities in liver function, renal function, or hematological examinations.

The ESL discontinuation rates were similar between the OXC-P and OXC-N groups (18.0% vs. 22.7%, P=0.886) (Table 2). Reasons for discontinuation also did not significantly differ between the two groups (ineffectiveness, 14.0% vs. 13.6%; AEs, 4.0% vs. 9.1%; P=0.685).

A summary of the efficacy, tolerability, and significant independent factors influencing a favorable response to ESL treatment in children and adolescents aged ≥6 years with focal epilepsy is presented in Fig. 2.

Discussion

This retrospective study demonstrated no significant difference in the rate of good response (≥50% reduction in seizure frequency) to ESL therapy between the OXC-P (switching from OXC to ESL) and OXC-N (adjunctive ESL therapy) groups (36.0% vs. 50.0%, P=0.214). Using multivariable logistic regression, a higher ESL maintenance dose (P=0.004), shorter duration of epilepsy (P=0.014), and fewer concomitant ASMs (P=0.034) were identified as independent significant factors influencing a good response to ESL treatment. No severe or life-threatening AEs were reported, and the discontinuation rate of ESL was similar in both groups (18.0% vs. 22.7%, P=0.886). To the best of our knowledge, this is the first real-world study based on clinical practice evaluating the effectiveness of switching from OXC to ESL or adding ESL as adjunctive therapy in pediatric patients with focal epilepsy at a single tertiary center in East Asia.

A previous study evaluated the efficacy and safety of converting CBZ treatment to ESL monotherapy in adult patients with treatment-resistant focal seizures [5]. The study reported that seizure frequency reduction and the proportion of ESL responders were numerically lower in patients previously treated with CBZ than in those who were not. A similar pattern emerged when data were analyzed according to prior use of any of four sodium channel blockers (CBZ, OXC, lamotrigine, or phenytoin) before converting to ESL monotherapy [5]. The effects associated with prior CBZ use may not have been specific to CBZ itself but rather to its mechanism of action (MOA). Generally, combinations of ASMs with different MOAs have been considered more effective than combinations of ASMs with similar MOAs. Nevertheless, in our study, ESL demonstrated efficacy regardless of whether OXC was included in the baseline ASM regimen before initiating ESL therapy (36.0% vs. 50.0%, P=0.214) (Fig. 1). Unlike other sodium channel blockers, such as OXC and CBZ, ESL does not influence the fast inactivation of VGSCs. Instead, ESL selectively enhances the slow inactivation of VGSCs, increasing the proportion of sodium channels unavailable for depolarization [17]. ESL has a predictable pharmacokinetic profile with high oral bioavailability, minimal protein binding, low potential for drug-drug interactions, and efficient renal clearance [17]. Additionally, ESL does not induce or inhibit cytochrome P450 enzymes according to preclinical and clinical studies [17]. Given these differences in MOAs, switching from OXC to ESL or adding ESL as adjunctive therapy may provide improved seizure control even when prior OXC treatment was less effective. Further prospective studies involving larger pediatric populations are necessary to elucidate mechanisms underlying seizure outcomes when transitioning from OXC to ESL.

Previously, a phase II, randomized, double-blind, placebo-controlled study in children (6 to 16 years old) with focal seizures showed ESL titrated up to 30 mg/kg/day effectively reduced seizures and was well-tolerated [11]. Additionally, a pooled analysis from phase III trials indicated adjunctive ESL (800 and 1,200 mg) effectively reduced seizures in patients with treatment-resistant focal seizures, irrespective of concurrent CBZ use [5]. In our study, responders—defined as having a ≥50% seizure frequency reduction—received significantly higher ESL maintenance doses (18.5±6.5 mg/kg/day vs. 14.8±4.5 mg/kg/day, P=0.001) compared to poor responders. Moreover, a higher maintenance ESL dose was an independent significant predictor of good response. The proportion of OXC-P patients was not significantly different between responders and poor responders (58.6% vs. 76.7%, P=0.169). Since our study excluded children who previously responded well to OXC, prior OXC use might not significantly influence ESL efficacy.

The outcome of this study was classified into good and poor responders to ESL treatment for seizure reduction, and comparative statistical analyses were performed on potential predictors (Table 3). Multivariable logistic regression, extending beyond simple logistic regression, was utilized to evaluate the relationship between a single binary outcome (response to ESL therapy) and multiple independent variables (predictors). This analysis confirmed the ESL maintenance dose (P=0.004), duration of epilepsy (P=0.014), and number of concomitant ASMs (P=0.034) as significant predictors of response (Table 4).

Since 2018, several studies have evaluated ESL efficacy and AEs in children and adolescents with epilepsy (Table 1). Most studies reported no significant difference in AE occurrence between ESL and placebo [11,13,14]. In our study, discontinuation rates did not differ significantly between the OXC-P and OXC-N groups, and no severe or life-threatening AEs were reported in either group.

Several limitations of this study should be acknowledged. First, compared with previous studies (Table 1), the present study included a relatively small sample size without a control group, although it was sufficient for statistical analysis. Despite this limitation, our study is the first real-world retrospective study in pediatric epilepsy patients. Second, the 6-month follow-up period used to evaluate efficacy was relatively short compared with previous studies. A longer observation period might better capture ESL efficacy. Third, serum ESL levels were not systematically measured, and the influence of dosage or serum concentrations of other ASMs on ESL efficacy was not assessed. Fourth, differences in ESL dosage may have influenced tolerability outcomes, which might not have been fully captured in this study. Lastly, behavioral or neurocognitive effects of ESL were not evaluated as potential AEs. Further large-scale, prospective studies involving younger children or infants with focal epilepsy are necessary to clarify ESL benefits in these populations.

In conclusion, our retrospective study demonstrated that switching from OXC to ESL and adjunctive ESL therapy were both efficacious and well-tolerated in children aged ≥6 years with focal epilepsy. The response rates to ESL were similar regardless of whether OXC was included in the baseline ASM regimen before initiating ESL therapy. No significant differences were found between groups regarding the rate or type of AEs. Significant factors associated with good response to adjunctive ESL therapy included higher ESL maintenance doses, shorter epilepsy duration, and fewer concomitant ASMs. Therefore, early use of ESL may be beneficial not only as adjunctive therapy in children who have not previously received sodium channel blockers, but also in those who have shown insufficient response to OXC.

Conflicts of interest

Sang Ook Nam is an editorial board member of the journal, but he was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Author contribution

Conceptualization: SL and YJL. Data curation: SL, JK, TJL, and YJL. Formal analysis: SL, JK, TJL, YMK, and GMY. Funding acquisition: YJL. Methodology: JK, SON, TJL, and YJL. Project administration: SON and YJL. Writing - original draft: SL and YJL. Writing - review & editing: SON, YMK, GMY, and YJL.

Acknowledgments

This study was supported by a 2024 research grant from Pusan National University Yangsan Hospital.

Fig. 1.

Reduction rate of seizure frequency between the oxcarbazepine (OXC)-P and OXC-N groups (OXC-P group, patients taking baseline anti-seizure medications including OXC; OXC-N group, patients previously taking other anti-seizure medications; responders, patients with ≥50% reduction in seizure frequency).

Fig. 2.

Summary of the efficacy and tolerability of eslicarbazepine acetate (ESL), as well as independent factors for seizure outcomes of ESL in pediatric patients aged ≥6 years with focal epilepsy. AE, adverse event; ASM, anti-seizure medication.

Table 1.

Previous studies on eslicarbazepine acetate therapy in children and adolescents

Study	Jozwiak et al. (2018) [11]	Veggiotti et al. (2018) [15]	Kirkham et al. (2020) [1]	Sankar et al. (2020) [14]	Mintz et al. (2020) [13]	Nyakeri et al. (2025) [16]
Design/countries	Study 208,	From study 208	Study 305	From study 208 & 305	From study 208 & 305	Retrospective cohort study
Design/countries	Phase II, DB-RCT/ Italy, Poland, Russia, Ukraine	2-yr OLE of phase II study	Phase III, DB-RCT/ 20 from Europe (17) & Asia (3; Malaysia, Philippines, Taiwan)	From study 208 & 305	DB-RCT	Retrospective cohort study
No. of participants	123 (2:1 to ESL:placebo)	42 (31=completed 2-yr OLE)	134:129 (ESL:placebo)	337 for 1 yr, 177 for 2 yr	362 (202:160=ESL:placebo)	50
Age	6−16 yr	6−16 yr	2−18 yr	4−17 yr	4−17 yr	3−19 yr
Seizures	F (≥2 in mo)	F (≥4 in mo)	F (≥4 in mo)	F (≥4 in mo)	F (≥2-4 in mo)	F, drug-resistant (daily to monthly)
Epilepsy duration	≥12 mo	≥12 mo	≥6 mo	≥6−12 mo	≥6−12 mo
No. of ASMs applied	1−2 (except OXC)	1−2 (except OXC)	1−2 (except OXC)	≥1−2 (except OXC)	1−2 (except OXC)	0-14 (including CBZ or OXC)
Duration of study	12 wk+1-yr OLE	Median retention times: 738 days	18 wk	1-yr OLE, and post-1-yr OLE	18 wk	At least 3 yr
Main results	No difference in CDR scores and TEAEs between placebo and ESL	≥1 TEAE in 7 patients	Greater reduction of seizure in patients ≥6 yr old with ESL 30 mg/kg/day than them of placebo	TEAEs: 64.1% (1-yr OLE) vs. 52.5% (post-1-yr OLE).	Similar incidence of TEAEs between ESL (67.8%) & placebo (65.6%).	TEAEs: 48.0% (no SAEs)
Main results		≥1 TEAE in 7 patients		Discontinuation due to TEAEs: 4.2% (1-yr OLE) vs. 0.6% (post-1-yr OLE)	SAEs: higher with ESL vs. placebo (9.9% vs. 5.0%)	≥50% seizure reduction: 30% (15/50)

DB-RCT, double-blind randomized placebo-controlled trial; OLE, open-label extension; ESL, eslicarbazepine acetate; F, focal-onset; ASM, anti-seizure medication; OXC, oxcarbazepine; CBZ, carbamazepine; CDR, cognitive drug research; TEAE, treatment-emergent adverse event; SAE, serious adverse event.

Table 2.

Comparison of demographic profiles and clinical features between OXC-P and OXC-N groups

Variable	Total (n=72)	OXC-P (n=50)	OXC-N (n=22)	P value
Male	45 (62.5)	29 (58.0)	16 (72.7)	0.355
Seizure type				0.866
Dyscognitive only	13 (18.1)	9 (18.0)	4 (18.2)
Focal motor/somatosensory	39 (54.2)	28 (56.0)	11 (50.0)
Focal with secondarily generalization	20 (27.8)	13 (26.0)	7 (31.8)
Lennox-Gastaut syndrome	11 (15.3)	5 (10.0)	6 (27.3)	0.128
Intellectual disability	21 (29.2)	14 (28.0)	7 (31.8)	0.407
Etiology				0.312
Genetic/metabolic	3 (4.2)	1 (2.0)	2 (9.1)
Infection	7 (9.7)	4 (8.0)	3 (13.6)
Structural	23 (31.9)	15 (30.0)	8 (36.4)
Unknown	39 (54.2)	30 (60.0)	9 (40.9)
Ketogenic diet	2 (2.8)	1 (2.0)	1 (4.5)	0.965
Vagus nerve stimulation	2 (2.8)	2 (4.0)	0	0.863
Age at seizure onset (yr)	6.8±4.0	6.6±3.6	7.3±4.8	0.437
Duration of epilepsy (yr)	3.2±1.5	3.2±1.5	3.1±1.3	0.728
Seizure frequency (/mo)	15.2±24.3	14.6±27.7	16.6±13.8	0.681
Age at ESL start (yr)	10.9±5.2	10.7±4.7	11.4±5.9	0.527
6−11	46 (63.9)	34 (68.0)	12 (54.5)	0.407
≥12	26 (36.1)	16 (32.0)	10 (45.5)
Duration of ESL therapy (mo)	6.1±3.7	6.0±3.3	6.3±2.9	0.294
Maintenance dose of ESL (mg/kg/day)	16.3±5.6	15.7±5.5	17.6±5.8	0.140
No. of concomitant ASMs	2.1±1.3	2.1±1.4	2.2±0.9	0.556
Retention rate				0.886
Maintenance	58 (80.6)	41 (82.0)	17 (77.3)
Discontinuation	14 (19.4)	9 (18.0)	5 (22.7)
Causes of discontinuation				0.685
Ineffective	10 (13.9)	7 (14.0)	3 (13.6)
Adverse events	4 (5.6)	2 (4.0)	2 (9.1)

Values are presented as number (%) or mean±standard deviation.

OXC, oxcarbazepine; OXC-P, patients with baseline ASMs regimens including OXC; OXC-N, patients with previously other ASMs without OXC; ESL, eslicarbazepine acetate; ASM, anti-seizure medication.

Table 3.

Comparison of demographics and outcomes between responders and poor responders to eslicarbazepine treatment

Variable	Responders (n=29)	Poor responders (n=43)	P value
Male sex	18 (62.1)	27 (62.8)	0.971
Seizure type			0.375
Dyscognitive only	7 (24.1)	6 (14.0)
Focal motor/somatosensory	13 (44.8)	26 (60.5)
Secondarily generalization	9 (31.0)	11 (25.6)
Lennox-Gastaut syndrome	6 (20.7)	5 (11.6)	0.475
Intellectual disability	7 (24.1)	19 (44.2)	0.137
Etiology			0.701
Genetic/metabolic	2 (6.9)	1 (2.3)
Infection	2 (6.9)	5 (11.6)
Structural	10 (34.5)	13 (30.2)
Unknown	15 (51.7)	24 (55.8)
Age at seizure onset (yr)	7.3±3.0	6.5±3.1	0.277
Duration of epilepsy (yr)	2.5±1.4	3.6±1.7	0.002^a
<3	22 (75.9)	14 (32.6)	0.001^a
3−7	7 (24.1)	29 (67.4)
Seizure frequency (/mo)	9.7±16.3	18.9±27.7	0.085
Age at ESL start (yr)	10.7±3.8	11.0±3.7	0.776
Maintenance dose of ESL (mg/kg/day)	18.5±6.5	14.8±4.5	0.001^a
<15	6 (20.7)	27 (62.8)	0.001^a
≥15	23 (79.3)	16 (37.2)
No. of concomitant ASMs	1.5±0.8	2.5±1.4	0.001^a
1−2	26 (89.7)	23 (53.5)	0.003^a
≥3	3 (10.3)	20 (46.5)
ASMs including OXC	17 (58.6)	33 (76.7)	0.169

Values are presented as number (%) or mean±standard deviation.

ESL, eslicarbazepine acetate; ASM, anti-seizure medication; OXC, oxcarbazepine.

^aP<0.05.

Table 4.

Multivariable logistic regression model for independent factors affecting the likelihood of a good response to eslicarbazepine adjunctive therapy in pediatric focal epilepsy

Factor	Estimate	z value	P value	OR (95% CI)
OXC-P	-1.5221	-1.94	0.052	0.22 (0.04-1.94)
Intellectual disability	-1.4944	-2.04	0.075	1.46 (0.14-12.06)
Seizure frequency (≥15/mo vs. <15/mo)	-0.1483	-0.14	0.885	0.86 (0.11-6.78)
No. of concomitant ASMs (≥3 vs. 1−2)	-1.9867	-2.12	0.034^a	0.14 (0.02-0.73)
Duration of epilepsy (≥3 yr vs. <3 yr)	-1.7069	-2.46	0.014^a	0.18 (0.04-0.67)
Dose of ESL (≥15 mg/kg/day vs. <15 mg/kg/day)	1.9793	2.91	0.004^a	7.24 (2.04-30.71)

OR, odds ratio; CI, confidence interval; OXC-P, baseline ASMs including oxcarbazepine; ASM, anti-seizure medication; ESL, eslicarbazepine acetate.

^aP<0.05.

Table 5.

Adverse events and profiles of eslicarbazepine treatment between the OXC-P and OXC-N groups in pediatric focal epilepsy

Variable	Total (n=72)	OXC-P (n=50)	OXC-N (n=22)	P value
AE	21 (29.2)	15 (30.0)	6 (27.3)	0.981
Dose of ESL at AEs appearance (mg/kg/day)	12.7±10.2	13.2±9.7	11.4±8.5	0.087
Type of AEs
Somnolence	9 (12.5)	6 (12.0)	3 (13.6)	0.871
Headache	7 (9.7)	5 (10.0)	2 (9.1)	0.901
Dizziness	6 (8.3)	5 (10.0)	1 (4.5)	0.758
Nausea	5 (6.9)	3 (6.0)	2 (9.1)	0.891
Fatigue	4 (5.6)	3 (6.0)	1 (4.5)	0.923
Anxiety	2 (2.8)	2 (4.0)	0	0.863
Insomnia	1 (1.4)	1 (2.0)	0	0.815

Values are presented as number (%) or mean±standard deviation.

OXC, oxcarbazepine; OXC-P, patients with baseline anti-seizure medication (ASM) regimens including OXC; OXC-N, patients with previously other ASMs without OXC; AE, adverse event; ESL, eslicarbazepine acetate.

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