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Objectives: To evaluate long-term efficacy, safety, and tolerability, including behavior and executive functioning, during adjunctive lacosamide (LCM) treatment in pediatric patients (≥1 month to <18 years of age) with focal-onset or generalized seizures enrolled in 2 open-label, long-term follow-up trials., Methods: Two open-label extension trials (SP848: NCT00938912; EP0034: NCT01964560) were conducted in pediatric patients who had participated in previous trials of adjunctive LCM (SP0847/NCT00938431; SP0966/NCT01969851; EP0060/NCT02710890; SP0967/NCT02477839; SP0969/NCT01921205); SP848 also directly enrolled eligible pediatric patients who had not previously participated in a clinical trial of LCM. Outcomes included retention, efficacy, and safety/tolerability. Patient improvement was assessed with Clinician's and Caregiver's Global Impression of Change scale. Behavior and emotional function was assessed with Achenbach Child Behavior Checklist (CBCL) and executive functioning was assessed with Behavior Rating Inventory of Executive Function® (BRIEF)., Results: The pooled dataset from both trials included 905 patients (851 in the focal-onset seizure population and 47 in the generalized seizure population). In the overall population, Kaplan-Meier-estimated 1-year retention was 80 %. From baseline to the end of the treatment period, patients in the focal-onset seizure population had a median percent reduction in focal-onset seizure frequency per 28 days of 60.4 %, 55.4 % of patients were 50 % responders, and 40.8 % of patients were 75 % responders. In patients with ≥12 months of LCM treatment, ≥12 month seizure freedom during the LCM treatment period was achieved by 29.9 % of patients in the focal-onset seizure population (median duration of first ≥12-month seizure-free interval: 641 days) and 24.4 % of patients in the generalized seizure population (median duration of first ≥12-month seizure-free interval: 665 days). Improvement during LCM treatment was reported in >75 % of patients by both physicians and caregivers. Treatment-emergent adverse events (TEAEs) were reported by 749 (82.8 %) patients, most commonly pyrexia (18.9 %), upper respiratory tract infection (18.6 %), nasopharyngitis (16.2 %), vomiting (15.7 %), and somnolence (11.8 %). The most common drug-related TEAEs were somnolence (8.5 %), dizziness (7.6 %), and vomiting (5.4 %). Behavioral and emotional function was generally stable in patients 1.5-5 years of age and slightly improved in patients ≥6 years of age, and executive functioning was stable in patients <5 years of age and generally slightly improved in patients 5-18 years of age., Conclusions: In this analysis of a large patient pool from 2 open-label trials, long-term adjunctive LCM was efficacious and generally well tolerated in children with epilepsy and focal-onset or generalized seizures. Behavior and executive functioning were generally stable without observable worsening during long-term adjunctive LCM treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MK Farkas and I Makedonska report no conflicts of interest. C Beller, D Bourikas, S Dimova, F Floricel, C McClung, and B Moseley are salaried employees of UCB Pharma and have received UCB Pharma stocks from their employment. C de la Loge (PCOM Analytics, Avallon, France) is contracted by UCB Pharma. S Therriault was an employee of UCB Pharma at the time the trials were conducted. JE Pina-Garza has served as a consultant and speaker for Catalyst Pharmaceuticals, Jazz Pharmaceuticals, Marinus Pharmaceuticals, Neurelis, SK Life Science, and UCB Pharma; and received payment from Elsevier for services as book editor., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The effect of adjunctive brivaracetam on health-related quality of life (HRQoL) was assessed in a post-hoc analysis using pooled data from three randomized, double-blind, placebo-controlled Phase III studies in patients with refractory focal seizures (NCT00490035, NCT00464269, and NCT01261325)., Methods: The Patient-Weighted Quality of Life in Epilepsy Questionnaire (QOLIE-31-P) was completed at randomization, and weeks 4, 8 (in two of three studies), and 12 (end of the treatment period). Mean change from baseline to week 12 or early discontinuation, and percentage of patients with clinically meaningful improvement were reported for the placebo and brivaracetam 50, 100, and 200mg/day groups., Results: At baseline, mean QOLIE-31-P scores were similar between treatment groups. At week 12 or early discontinuation, mean (standard deviation) changes from baseline in QOLIE-31-P total score were 2.8 (12.7), 3.0 (14.0), 2.4 (14.0), and 3.0 (12.1) points for the placebo and brivaracetam 50, 100, and 200mg/day groups, respectively, indicating HRQoL improved slightly over time during the treatment period, but was similar for placebo and brivaracetam groups. All subscale score changes were positive, indicating stable or improved HRQoL over time. The brivaracetam 100 and 200mg/day groups showed the largest differences compared with placebo in Seizure Worry subscale scores (7.3 and 8.8 vs. 5.0 points). Approximately 40% of patients had improvements in QOLIE-31-P scores beyond the Minimal Important Change (MIC) thresholds. The subgroup of ≥50% focal seizure frequency responders had higher improvements for all treatment arms and all subscales than for those in the overall pooled population., Conclusion: In this post-hoc analysis, adjunctive brivaracetam treatment was shown to be associated with stable or improving overall HRQoL over time, similar to placebo, with modest improvements in subscales sensitive to efficacy, and no deterioration in subscales sensitive to tolerability. These results reflect the known efficacy and tolerability profile of brivaracetam., (Copyright © 2016 Ellen Carey, UCB Brussels, Belgium. Published by Elsevier Inc. All rights reserved.)

Objective: The online PatientsLikeMe® Epilepsy Community allows patients with epilepsy to record, monitor, and share their demographic, disease, and treatment characteristics, providing valuable insights into patient perceptions and understanding of epilepsy. The objective of this retrospective analysis was to characterize the profile of users and their disease and identify factors predictive of poor health-related quality of life (HRQoL), while assessing the platform's potential in providing patient-reported data for research purposes., Methods: Data recorded (January 2010-November 2011) by Epilepsy Community members, with an epilepsy diagnosis and who reported >1 seizure, included the following: sociodemographic and disease characteristics, treatments, symptoms, side effects perceived as medication-related, seizure occurrence, and standardized questionnaires (Quality of Life in Epilepsy Inventory [QOLIE-31/P], EuroQoL 5-Dimensions Scale, 3 Levels [EQ-5D-3L], and Hospital Anxiety and Depression Scale [HADS]). Univariate and multivariate logistic regressions were conducted to identify predictors of poor HRQoL., Results: During the study period, the Epilepsy Community comprised 3073 patients, of whom 71.5% were female, had a mean age of 37.8years, and had a mean epilepsy duration of 17.7years. The most frequently reported moderate/severe symptoms (n=2135) included memory problems (60.2%), problems concentrating (53.8%), and fatigue (50.0%). Medication-related side effects (n=639) included somnolence (23.2%), fatigue (17.2%), and memory impairment (13.8%). The QOLIE-31/P scores (n=1121) were significantly worse in patients who experienced a recent seizure. For QOLIE-31/P, highly predictive factors for poor HRQoL included the following: mild/moderate problems concentrating, depression, memory problems, treatment side effects, occurrence of tonic-clonic seizures, and epilepsy duration ≤1year. For EQ-5D-3L, highly predictive factors for poor HRQoL included the following: pain, depression, and comorbidities. Patients on newer AEDs were less likely to report poor HRQoL (QOLIE-31/P)., Significance: These findings move further towards supporting the feasibility and usefulness of collecting real-world, anonymized data recorded by patients online. The data provide insights into factors impacting HRQoL, suggesting that a holistic treatment approach beyond seizure control should be considered in epilepsy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The sensitivity of the Seizure Severity Questionnaire (SSQ) was evaluated using pooled data from open-label extensions of two clinical trials in patients with partial-onset seizures. The SSQ includes questions relating to frequency and helpfulness of warning signs as well as frequency, severity, and bothersomeness of ictal and postictal effects. Differences between mean change from baseline for each SSQ item for responders and nonresponders were described and compared between patients solely with complex partial seizures (CPSs: responders, n=166; nonresponders, n=127) and those solely with secondarily generalized partial seizures (SGPSs: responders, n=26; nonresponders, n=24) at baseline. Seizure Severity Questionnaire total score and individual SSQ items related to ictal movement, consciousness, bothersomeness of postictal effects, and frequency of postictal emotional effects showed differentiation between seizure type responders. These data provide further validation of the SSQ by demonstrating its sensitivity in describing treatment effects., (© 2013.)

The Seizure Severity Questionnaire (SSQ) was developed to evaluate changes in seizure severity and bothersomeness. Determination of a threshold value reflecting meaningful patient benefit on the SSQ would improve clinical interpretation of scale results. The objective of this analysis was to define a minimally important change (MIC) threshold for the SSQ, using data from patients with treatment-resistant partial-onset seizures from two clinical trials (N=776). Minimally important change thresholds were calculated using standard anchor-based methods, with the Patient Global Impression of Change (PGIC) score as the anchor with the categories of 'much improved,' 'minimally improved,' 'much worsened,' and 'minimally worsened' combined. The calculated MIC thresholds (range: 0.34 to 0.50) suggest that a 0.48-point change in the SSQ total score reflects a clinically meaningful change in seizure severity from the patients' perspective., (© 2013 Elsevier Inc. All rights reserved.)

The Quality of Life Inventory in Epilepsy (QOLIE-31) is a valuable tool to assess the impact of antiepileptic drugs on patients' lives, but interpretation of mean score changes can be challenging. Minimally important change (MIC) thresholds can be used to describe the proportion of clinically improved or worsened patients. Pooled data from Phase II/III trials of adjunctive lacosamide in patients with treatment-resistant partial-onset seizures were used to estimate MIC thresholds for the QOLIE-31 total score and subscales. Using multiple distribution- and anchor-based estimation methods, the optimal MIC value for the total score in this population of patients with treatment-resistant seizures was 5 points, which is lower than those previously reported in the literature for mixed populations. MIC estimates varied substantially across QOLIE-31 subscales. Taken together, these results demonstrate that intrinsic characteristics of a patient population impact what should be considered as MIC, a key consideration in the clinical interpretation of QOLIE-31 change scores., (Copyright © 2012 Elsevier Inc. All rights reserved.)

An epilepsy community was developed on PatientsLikeMe.com to share data between patients to improve their outcomes by finding other patients like them. In a 14-day response period, 221 patients with epilepsy (mean age: 40 years, SD: 12, range: 17-72, 66% female) completed a survey about benefits they perceived. Prior to using the site, a third of respondents (30%) did not know anyone else with epilepsy with whom they could talk; of these, 63% now had at least one other patient with whom they could connect. Perceived benefits included: finding another patient experiencing the same symptoms (59%), gaining a better understanding of seizures (58%), and learning more about symptoms or treatments (55%). Number of benefits was associated with number of relationships with other patients, F(4,216)=8.173, P<0.001). Patients with epilepsy reported an array of perceived benefits similar to those reported by populations with other diseases. Controlled sharing of health data may have the potential to improve disease self-management of people with epilepsy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A randomized, double-blind, placebo-controlled study (N01103, NCT00105040) evaluated behavioral and emotional effects of adjunctive levetiracetam (LEV) treatment in children and adolescents (4-16years old) with uncontrolled partial-onset seizures. Patients received adjunctive LEV 20-60mg/kg/day (n=64) or placebo (n=34) for 12weeks. The Achenbach Child Behavior Checklist (CBCL) and portions of the Child Health Questionnaire-Parent Form 50 (CHQ-PF50) were used to assess behavioral and emotional functioning at baseline and end of the treatment period. Worsening of the mean CBCL Aggressive Behavior score occurred for LEV but not placebo, leading to similar results for Externalizing Syndromes and Total Problems (all P<0.05 vs placebo). The change in the CBCL Activities Competence score favored LEV (P<0.05). These results are in line with the known safety profile of LEV., (Copyright 2010 Elsevier Inc. All rights reserved.)