AIMS:To find out which variables may be associated with comfort of patients in an epilepsy monitoring unit.DESIGN:Exploratory, quantitative study design.METHODS:Data were collected from October 2018 to November 2019 in Austria and Southern Germany. A total of 267 patients of 10 epilepsy centres completed the Epilepsy Monitoring Unit Comfort Questionnaire which is based on Kolcaba's General Comfort Questionnaire. Secondary data analysis were conducted by using descriptive statistics and an exploratory model building approach, including different linear regression models and several sensitivity analyses.RESULTS:Total comfort scores ranged from 83 to 235 points. Gender, occupation and centre turned out to be possible influential variables. On average, women had a total comfort score 4.69 points higher than men, and retired persons 28.2 points higher than high school students ≥18 years. Comfort scores of younger patients were lower than those of older patients. However, age did not show a statistically significant effect. The same could be observed in marital status and educational levels.CONCLUSION:When implementing comfort measures, nurses must be aware of variables which could influence the intervention negatively. Especially, high school students ≥18 years should be supported by epilepsy specialist nurses, in order to reduce uncertainty, anxiety and discomfort. But, since the identified variables account only for a small proportion of the inter-individual variability in comfort scores, further studies are needed to find out additional relevant aspects and to examine centre-specific effects more closely.IMPACT:Nurses ensure patient comfort during a hospital stay. However, there are variables that may impair the effectiveness of the nursing measures. Our study showed that the experience of comfort was highly individual and could be explained by sociodemographic variables only to a limited extent. Nurses must be aware that additional factors, such as the situation in the individual setting, may be relevant.

A third of patients with epilepsy worldwide are in need of more effective anticonvulsive drugs, since their epileptic seizures remain uncontrolled with currently available medical treatments. 1 Kwan P Brodie MJ Early identification of refractory epilepsy. N Engl J Med. 2000; 342: 314-319 Crossref PubMed Scopus (3709) Google Scholar To date, despite that a dozen new drugs have been developed in the past 20 years, the chance of complete seizure control after failure of two anticonvulsant treatments, even in patients with newly diagnosed epilepsy, is low. 2 Chen Z Brodie MJ Liew D Kwan P Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018; 75: 279-286 Crossref PubMed Scopus (570) Google Scholar In The Lancet Neurology, Gregory Krauss and colleagues 3 Krauss GL Klein P Brandt C et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2019; (published online Nov 13)https://doi.org/10.1016/S1474-4422(19)30399-0 Summary Full Text Full Text PDF PubMed Scopus (97) Google Scholar report results of the second phase 2 double-blind, randomised, placebo-controlled, dose-response trial on the safety and efficacy of adjunctive cenobamate (YKP3089) for the treatment of focal epilepsy. The mechanism of action of this drug is still under investigation. Beside inhibiting excitatory sodium-channel currents, it is believed that cenobamate enhances inhibition by modulation of GABAA receptors. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trialAdjunctive cenobamate reduced focal (partial)-onset seizure frequency, in a dose-related fashion. Treatment-emergent adverse events were most frequent in the highest dose group. Cenobamate appears to be an effective treatment option in patients with uncontrolled focal seizures. Full-Text PDF Correction to Lancet Neurol 2020; 19: 23–24Arnold S. Cenobamate: new hope for treatment-resistant epilepsy. Lancet Neurol 2020; 19: 23–24—In this comment, the last line of paragraph two should read "patients with treatment-resistant epilepsy". This correction has been made to the online version as of Dec 11, 2019, and will be made to the printed version. Full-Text PDF

Purpose: The purpose of the study was to evaluate the psychometric properties of the newly developed Epilepsy Monitoring Unit Comfort Questionnaire (EMUCQ) according to the consensus-based standards for the selection of health measurements instruments (COSMIN). Moreover, we aimed to assess changes in comfort-levels. Methods: From October 2018 to November 2019, a total of 267 patients participated in a quantitative study in ten epilepsy centers in Austria and southern Germany. For basic item analysis, descriptive analysis and correlational analysis were computed. An exploratory factor analysis (EFA) was undertaken to detect the factor structure. Reliability was checked through internal consistency (Cronbach's alpha) and the measurement error. In the validity domain, convergent validity and structural validity were estimated. t-Tests were used to detect changes in comfort-levels. Results: Due to unfavorable statistical properties, two items were removed. Exploratory factor analysis showed a three-factorial solution. The EMUCQ was found to be a reliable instrument (Cronbach's alpha 0.77-0.81 for the subscales, 0.88 for the scale total comfort); convergent validity could be supported, too. Confirmatory factor analysis (CFA) supported the hypothesis that structural validity for the three subscales holds. The patients' comfort levels were lower at the end of the stay than at the beginning and lower in nonseizure free patients compared with seizure-free patients. Conclusion: Validity and reliability are supported for the 42-item EMUCQ in the three-factorial solution. Owing to the item reduction and modifications made in the CFA, a new test should be carried out on a different sample. (C) 2020 Elsevier Inc. All rights reserved.

BACKGROUND:This long-term follow-up (LTFU) trial was conducted to evaluate the long-term safety and tolerability of brivaracetam (BRV) at individualized doses (maximum of 200 mg/day) in patients with focal seizures. The secondary objective was to evaluate the efficacy of BRV over time. METHODS:Two Phase III, randomized, double-blind, historical-controlled conversion-to-monotherapy trials (N01276: NCT00698581; N01306: NCT00699283) were conducted in patients aged ≥16 years with uncontrolled focal seizures. Patients who completed either of these core trials or who met a protocol-defined exit criterion could enter this LTFU trial (N01315; NCT00761774). Patients entered LTFU at a recommended BRV dose of 100 mg/day, with flexible dosing of 50-200 mg/day, as monotherapy or adjunctive therapy; additional AEDs could be prescribed and adapted in dose if clinically indicated. Safety variables included treatment-emergent adverse events (TEAEs). Efficacy variables included duration of continuous monotherapy, reduction in focal seizure frequency and seizure freedom. Safety and efficacy variables were assessed for all patients in the safety set or efficacy set, respectively, regardless of BRV treatment regimen. In addition, a post hoc subgroup analysis was conducted for patients who completed the BRV monotherapy period in either core trial, and entered the LTFU on BRV monotherapy. For this subgroup, TEAEs were summarized by 3-month time intervals over the first 12 months of LTFU. RESULTS:108 patients were enrolled in the LTFU trial between November 2008 and February 2010. 79 (73.1 %) patients discontinued the LTFU trial, most commonly due to lack of efficacy [37 (34.3 %)] and adverse events [16 (14.8 %)]. At core trial baseline, patients had a median of 6.3 focal seizures/28 days and 53 (49.1 %) had failed ≥5 previous lifetime AEDs. During LTFU, 70 (64.8 %) patients had ≥12 months and 56 (51.9 %) patients had ≥24 months of BRV treatment. TEAEs were reported by 98 (90.7 %) patients; most commonly (≥15 % of patients) convulsion (17.6 %), nasopharyngitis (17.6 %), depression (16.7 %) and fatigue (15.7 %). Median percent reduction from baseline in focal seizure frequency/28 days was 56.8 %. Among 86 patients who completed at least 6 months of treatment, 29 (33.7 %) patients were seizure-free for ≥6 months and 22 (25.6 %) were seizure-free for ≥12 months. 50/108 patients were included in the BRV monotherapy subgroup; 33/50 (66.0 %) patients reported a TEAE in the core trials, while 26/50 (52.0 %), 15/37 (40.5 %), 14/33 (42.4 %) and 9/27 (33.3 %) patients reported any TEAE during LTFU months 1-3, 4-6, 7-9 and 10-12, respectively. In the BRV monotherapy subgroup, the most common TEAEs (≥5% of patients) during LTFU months 1-3 were fatigue [3/50 (6.0 %)] and dizziness [3/50 (6.0 %)]. INTERPRETATION:Results from the LTFU trial support the long-term safety of BRV at individualized doses of up to 200 mg/day as a well-tolerated, and effective treatment for patients with focal seizures. Efficacy analyses indicate that seizure reductions with brivaracetam were generally maintained over time.

1Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Vogtareuth, Germany 2Research Institute for Rehabilitation, Transition and Palliation, PMU Salzburg, Austria 3Comprehensive Epilepsy Program for Children, Division of Pediatric Neurology, DevelopmentalMedicine and Social Pediatrics, Department of Pediatrics, University Hospital Munich, Munich, Germany 4Epilepsy Unit for Adult Patients, Schön Klinik Vogtareuth, Vogtareuth, Germany

Abstract Introduction Effects of antiepileptic drug (AED) load changes in patients with focal seizures have not been well evaluated. Methods SP1065 (NCT01673282) was a noninterventional, prospective, observational study conducted in a clinical practice setting. Patients (aged ≥18 years) with focal seizures were enrolled within 7 days of being prescribed adjunctive lacosamide. Observation period was ~6 months. Drug load was assessed using percentage change in ratio of actual prescribed dose and World Health Organization defined daily dose (DDD) for concomitant AEDs and all AEDs (including lacosamide). Subgroups were defined for patients with at least one concomitant sodium channel–blocking AED (SCB [+]) and those without (SCB [−]). Results A total of 311 patients were assessed for safety, 302 for measurement of drug load, and 240 for effectiveness. Ratio of AED dose to DDD decreased for concomitant AEDs (−9.6%) and increased for all AEDs (including lacosamide; 15.5%). Median reduction in focal seizure frequency per 28 days was 100% (range: −100, 2275.8). 70.4% and 61.7% of patients had a ≥50% or ≥75% reduction in seizure frequency, respectively; 50.8% became seizure‐free. In the SCB (+) subgroup (n = 149), ratio of AED dose to DDD decreased for concomitant AEDs (−15.0%) and increased for all AEDs (10.7%). In the SCB (−) subgroup (n = 153), ratio of AED dose to DDD decreased for concomitant AEDs (−4.4%) and increased for all AEDs (20.2%). Fifty‐seven patients (18.3%) reported ADRs, most commonly dose >400 mg/d (7.1%). Seventeen patients (5.5%) had ADRs leading to discontinuation. Significance Addition of lacosamide resulted in reduction of concomitant AED drug load regardless of whether concomitant AEDs were SCB (+) or SCB (−). These results indicate that addition of lacosamide in patients with focal seizures could allow clinicians to withdraw or reduce the dose of less well‐tolerated or less effective AEDs.

SummaryObjectiveDepression and anxiety are highly prevalent among people with epilepsy (PwE) but often remain unrecognized and treated inadequately. Effective psychosocial treatments such as cognitive behavioral therapy (CBT) are rarely available to most PwE, which is one reason electronically delivered CBT (eCBT) is regarded as promising. This study examined an eCBT intervention, termed Emyna, that was tailored to suit the needs of PwE. It includes CBT‐related content on depression, stress and anxiety, seizure triggers and auras, and lifestyle habits. The trial examined the efficacy of Emyna in reducing symptoms of depression (primary outcome) and anxiety as well as improving quality of life.MethodsParticipants (N = 200) with epilepsy, a diagnosis of a depressive disorder, and at least moderate depressive symptoms were randomized to Emyna or care as usual. At baseline and after 3, 6, and 9 months, participants were invited to complete online questionnaires. The primary outcome was improvement of depressive symptoms at 3 months.ResultsRelative to the control group, intervention group participants experienced significantly greater improvements in depression, anxiety, stress, social‐occupational impairment, and epilepsy‐related quality of life, in both intention‐to‐treat (ITT) and per‐protocol analyses. In ITT analyses, effects of medium magnitude were observed, as measured by the Patient Health Questionnaire–9 items (Cohen d = 0.54, 95% confidence interval [CI] = 0.25‐0.82, P < 0.001) and the Neurological Disorders Depression Inventory for Epilepsy (d = 0.51, 95% CI = 0.23‐0.79, P < 0.01). At 3 months, intervention group participants also reported fewer illness‐related days off work and fewer days hospitalized over the preceding months, compared to control group participants (P ≤ 0.05), whereas no such differences were present at baseline (P > 0.30).SignificanceThese findings showed that Emyna, used adjunctively to usual care, could help improve mental health, social‐occupational functioning, and quality of life among PwE. The program provides an additional treatment option that could produce clinically relevant symptom reductions and reduce key cost drivers (ie, hospitalization rates and illness‐related inability to work).

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) approved for monotherapy (in the USA) and adjunctive treatment of focal (partial-onset) seizures in adults, at a dose range of 50-200 mg/day taken in two equal doses, with a recommended starting dose of 100 mg/day. Two Phase III, randomized, double-blind, multicenter, historical-controlled, conversion-to-mono therapy studies (N01276, NCT00698581; N01306, NCT00699283) were conducted to evaluate the efficacy, safety, and tolerability of conversion to BRV 50 mg/day monotherapy in adults with uncontrolled focal seizures. Patients aged 16-75 years, with 2-40 focal seizures per 4 weeks during an 8-week baseline, and on stable doses of 1-2 AEDs were enrolled. Patients were randomized to BRV 50 or 100 mg/day (3:1) in two equal doses without titration. The treatment period comprised 1-week BRV add-on, 8-week baseline AED tapering, and 8-week BRV monotherapy periods. Primary efficacy endpoint was Kaplan-Meier estimate of the cumulative exit rate due to pre-defined exit criteria at Day 112 (50 mg/day, efficacy population). The upper 95% confidence interval (CI) was compared with the historical control threshold (0.722). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs; intent-to-treat population). After randomization of 150 patients (N01276: 88; N01306: 62), both studies were terminated due to the confounding effects of a higher-than-expected discontinuation rate. For BRV 50 mg/day, 1 exit criterion was met by 26/67 (38.8%) patients (study N01276) and 18/45 (40.0%) patients (study N01306). In both studies, the cumulative exit rate was lower than the historical control threshold (N01276: 0.487, 95% CI 0.347, 0.626; N01306: 0.474, 95% CI 0.310, 0.638). However, with maximum 10% censoring due to early withdrawal (sensitivity analysis), cumulative exit rates were above historical control (N01276: 0.652, 95% CI 0.532, 0.772; N01306: 0.704, 95% CI 0.563, 0.844). Overall incidence of TEAEs was 110/150, 73.3% (treatment period); 78/147, 53.1% (baseline AED tapering period); 41/84, 48.8% (BRV monotherapy period). In conclusion, BRV 50 mg/day monotherapy demonstrated an exit rate lower than historical control. Results should be interpreted with caution as, following termination of both studies, patient numbers were too low to evaluate the efficacy of BRV monotherapy. These are the first published safety and tolerability data for BRV monotherapy. Monotherapy was well tolerated, with a relatively low incidence of TEAEs, though this should be interpreted with the caveat that the majority of common TEAEs were likely to have occurred earlier in the course of treatment with BRV. No new safety concerns were identified, supporting the favorable safety profile of BRV observed in adjunctive studies.

Im Rahmen der SANTE-Studie (7) konnte gezeigt werden, dass die Stimulation im Nucleus anterior des Thalamus (ANT) zu einer signifikanten Reduktion der Anfallshäufigkeit bei therapieschwieriger Epilepsie führt. Ebenfalls signifikante Effekte konnten auch bei der Stimulation des Hippocampus gezeigt werden (8,10,16,19,32) die aber in Deutschland bisher nicht etabliert ist. Andere Stimulationstargets spielen im breiteren klinischen Einsatz ebenfalls keine Rolle. Die vielversprechenden Ergebnisse der SANTE-Studie ließen sich nach nun siebenjähriger Anwendung in Deutschland nur teilweise reproduzieren. In diesem Artikel sollen mögliche Gründe für die von der SANTE-Studie abweichenden Ergebnisse analysiert und der aktuelle Stellenwert der Tiefen Hirnstimulation bei der therapieschwierigen Epilepsie diskutiert werden.

Background: Depression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet-administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual.Methods/Design: This randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3).Discussion: Results of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety.

SummaryObjectiveEvidence for the efficacy and safety of adjunctive lacosamide in the treatment of partial‐onset seizures (POS) was gained during placebo‐controlled clinical trials in patients with treatment‐resistant seizures who were taking one to three concomitant antiepileptic drugs (AEDs). The VITOBA study (NCT01098162) evaluated the effectiveness and tolerability of adjunctive lacosamide added to one baseline AED in real‐world clinical practice.MethodsWe conducted a 6‐month observational study at 112 sites across Germany. Adult patients (≥16 years) with POS received lacosamide adjunctive to only one baseline AED. Seizure frequency reduction at the end of the observation period was compared with a 3‐month retrospective baseline period.ResultsFive hundred seventy‐one patients received lacosamide at least once (Safety Set [SS]); 520 provided evaluable seizure records (Full Analysis Set [FAS]); and 499 took in‐label dosages of lacosamide (up to 400 mg) and were evaluated for effectiveness (modified FAS). Median baseline seizure frequency was 2.0 per 28 days: 47.1% of patients (235/499, mFAS) took a concomitant sodium channel–blocking (SCB) AED; 38.1% (190/499) had only one lifetime AED; and 18.4% (92/499) were aged ≥65 years (mFAS). At the final visit, 72.5% (358/494) of patients showed a ≥50% reduction in seizure frequency from baseline, 63.8% (315/494) showed a ≥75% reduction, and 45.5% (225/494) were seizure‐free. Seizure freedom rates were higher in patients aged ≥65 years (56.7%) compared with patients aged <65 years (43.1%), in patients with ≤5 years epilepsy duration (52.5%) versus >5 years duration (41.0%), and when added to first monotherapy (60.5%) rather than as a later therapy option. Treatment‐emergent adverse events (TEAEs) were reported by 48.5% (277/571) of patients (SS), with a profile similar to that observed in pivotal trials; 466 of patients (81.6%, SS) continued lacosamide therapy after the trial.SignificanceThese results suggest that lacosamide use, added to one concomitant AED, was effective at improving seizure control and was well tolerated in patients treated in routine clinical practice.

OBJECTIVE: To reflect actual medical care of epilepsy patients, this pre-specified analysis was conducted to document patient characteristics, treatment patterns, and effect of adjunctive lacosamide (LCM) on seizure control, by physician setting.BACKGROUND: The VITOBA study evaluated LCM seizure control and tolerability in patients with POS in a clinical setting receiving only one concomitant AED.DESIGN/METHODS: This 6-month, observational study (NCT01098162) in Germany targeted office-based neurologists (ON), hospital-based neurologists (HN) and specialized epilepsy centers (EC) at 6(ON):1(HN) and 4(ON):1(EC) ratios. Outcome variables included changes in seizure frequency (蠅50[percnt] and 蠅75[percnt] responder, and seizure freedom rates) during the final 3 months compared with a 3-month retrospective baseline, and adverse events (AEs). All analyses are descriptive. Efficacy analyses included patients treated with in-label LCM doses at any time (mFAS).RESULTS: 112 centers/investigators participated (ON=86, HN=14, EC=12). Of 573 enrolled patients, 499 (ON=345, HN=51, EC=103) comprised the mFAS. EC treated a more refractory population than ON/HN as indicated by a greater number of >6 previous AEDs (17.5[percnt], 2.9[percnt], 5.9[percnt], respectively), median epilepsy duration (12.0, 8.0, 3.0 years), and median seizure frequency/28 days at baseline (4.0, 2.0, 1.7 seizures). During the final 3 months, 52.0[percnt], 60.0[percnt], and 80.2[percnt] of EC-, HN-, and ON-treated patients showed a 蠅50[percnt] response to LCM; 40.0[percnt] EC-treated, 56.0[percnt] HN-treated, and 71.8[percnt] ON-treated patients showed a 蠅75[percnt] LCM response. 31.0[percnt], 38.0[percnt] and 50.9[percnt] of EC-, HN-, and ON-treated patients were seizure free. EC (64.8[percnt]) and HN (64.3[percnt]) reported more AEs than ON (41.2[percnt])(safety set N=571). 81.3[percnt] completed the study; 18.9[percnt] EC-treated, 8.9[percnt] HN-treated, and 8.4[percnt] ON-treated patients discontinued due to an AE.CONCLUSIONS: LCM add-on therapy to one AED improved seizure control and was generally well tolerated in routine clinical practice; seizure control differences between physician setting may be explained by differences in epilepsy characteristics.Study Supported by: UCB Pharma. Disclosure: Dr. Noack-Rink has received personal compensation for activities with UCB Pharma as an employee. Dr. Brandt has received personal compensation for activities with Otsuka, Eisai, and UCB Pharma as an advisory board and/or speaker. Dr. Mayer has received personal compensation for activities with UCB Pharma, Eisai Inc., and Deistin Arzneimittel GmbH as a consultant. Dr. Arnold has received personal compensation for activities with UCB Pharma, Upsher-Smith, and Eisai as a consultant. Dr. Runge has received personal compensation for activities with UCB Pharma and Eisai Inc. as a consultant. Dr. Ramirez has received personal compensation for activities with UCB Pharma as an employee. Dr. Lauterbach has received personal compensation for activities with UCB Pharma as an employee. Dr. Dedeken has received personal compensation for activities with UCB Pharma as an employee.

OBJECTIVE: To provide clinical data on elderly patients, this subgroup analysis evaluated the effect of adjunctive lacosamide (LCM) in elderly patients with partial-onset seizures (POS) receiving only one baseline AED in a real-life medical practice setting. BACKGROUND: Exclusion criteria limited recruitment of elderly patients in the LCM epilepsy pivotal trials; data in elderly epilepsy patients would be informative for clinical practice. DESIGN/METHODS: This subgroup analysis of the 6-month, observational VITOBA study (NCT01098162) in Germany compared data from the elderly (蠅65 years) and younger (<65 years) patient subgroups. Outcome variables included seizure freedom and reduction in seizure frequency (蠅50[percnt] and 蠅75[percnt] responder rates) during the final 3 months of the study compared with 3-month retrospective baseline, and adverse events (AEs). Descriptive efficacy analyses include full analysis set patients treated only with in-label doses of LCM at any time (mFAS). RESULTS: Of 573 enrolled patients, 92 (18.4[percnt]) patients in the mFAS (n=499) were elderly. Compared to younger patients, elderly patients had a lower baseline median seizure frequency/28 days (2.00 vs 2.33) and a shorter epilepsy duration (10.7 vs 14.2 years). More elderly patients were treated with 1 lifetime AED than younger patients (55.4[percnt] vs 34.2[percnt]). During the study's final 3 months, 81.1[percnt] elderly vs 70.5[percnt] younger patients showed a 蠅50[percnt] response and 77.8[percnt] elderly vs 60.6[percnt] younger patients showed a 蠅75[percnt] response to LCM; 56.7[percnt] elderly vs 43.1[percnt] younger patients were seizure free. Any AEs were reported by 45.5[percnt] of elderly and 49.2[percnt] of younger patients (safety set N=571); 8.2[percnt] vs 11.3[percnt] reported AEs leading to discontinuation. CONCLUSIONS: Adjunctive LCM to one baseline AED in elderly resulted in higher efficacy outcomes than in younger patients. Elderly patients, however, had a shorter disease duration. The AE pattern did not reveal a specific safety pattern in the elderly. Study Supported by: UCB Pharma.

OBJECTIVE: Assess the efficacy of USL255, once-daily extended-release topiramate, in patients subdivided by baseline seizure type and antiepileptic drug (AED) use. BACKGROUND: Seizure type, concomitant AED use, and the number of previous AEDs may influence responsiveness of a patient to AED treatment. These analyses attempt to identify effectiveness of USL255 in treatment-resistant patient subgroups. DESIGN/METHODS: In this double-blind, phase 3 study (PREVAIL; NCT01142193), patients with partial-onset seizures (POS) on 1-3 concomitant AEDs were randomized to placebo (n=125) or USL255 (n=124), titrated over 3 weeks (50 mg/week), and maintained at 200 mg/day for 8 weeks. Efficacy assessments included median percent reduction from baseline in weekly POS frequency and 50% responder rate. Subgroup analyses included efficacy by 1) POS seizure type, 2) concomitant AED use, 3) lifetime AED use, and 4) refractory status (‘highly refractory’, 蠅2concomitant AEDs and 蠅4 lifetime AEDs; ‘less refractory’, 1 concomitant AED or <4 lifetime AEDs), although PREVAIL was not powered for statistical analyses in these subgroups. RESULTS: In subjects experiencing disabling seizures (complex partial with/without secondary generalization), USL255 significantly reduced weekly seizure frequency (40.6% vs 17.7%; P P =.001) vs placebo. Both seizure reduction and responder rate were significantly improved in patients concurrently taking 蠅3 AEDs ( P P =.001 and .007, respectively). In patients deemed ‘highly refractory’, reduction in seizure frequency was 2-fold higher with USL255 vs placebo (40.4% vs 18.1%; P =.004) and responder rate was significantly improved (38.5% vs 19.0%; P =.023). CONCLUSIONS: USL255 was efficacious as an adjunctive treatment for POS, with a variety of concomitant AEDs, and in highly refractory patients. Results from the PREVAIL study demonstrate broad and consistent efficacy of USL255, which may provide a significant benefit to patients with epilepsy. Study Supported by: Upsher-Smith Laboratories, Inc. Disclosure: Dr. Blatt has received personal compensation for activities with Upsher-Smith and GlaxoSmithKline, Inc. Dr. Nagaraddi has received personal compensation for activities with Upsher-Smith Laboratories as a consultant, and with UCB Biosciences as a speaker. Dr. Nagaraddi has received research support from Upsher-Smith Laboratories and UCB Biosciences. Dr. Hogan has received research support from Eisai Inc., and Upsher Smith. Dr. Arnold has received personal compensation for activities with UCB Pharma, Upsher-Smith, and Eisai Inc. as a consultant. Dr. Lawson has received personal compensation for activities with Upsher-Smith Laboratories as a consultant. Dr. Lawson has received research support from Upsher-Smith Laboratories. Dr. Anders has received personal compensation for activities with Upsher-Smith Laboratories, Inc. Dr. Clark has received personal compensation for activities with Upsher-Smith Laboratories, Inc. Dr. Halvorsen has received personal compensation for activities with Upsher-Smith Laboratories, Inc. Dr. Halvorsen holds stock in Medtronic Inc., Stryker, Elan Corp., Teva Neuroscience, Gilead, Pfizer Inc., and Amgen Inc. Dr. Chung has received personal compensation for activities with UCB Pharma, Supermus, Esai Inc., Lundbeck Research USA, Inc., Upshire-Smith, and SK Life Science.

OBJECTIVE: Evaluate the adverse event profile of USL255, once-daily extended-release (XR) topiramate, in adults with refractory partial-onset seizures (POS). BACKGROUND: Treatment-emergent adverse events (TEAEs) affecting the central nervous system can be associated with antiepileptic drug (AED) treatment. Immediate-release (IR) topiramate is an AED that is efficacious for the management of epilepsy, but requires twice-daily dosing. USL255 can be given once daily, is pharmacokinetically equivalent to IR topiramate at the same daily dose, and has reduced plasma fluctuations, which may result in decreased incidence of TEAEs caused by high peak drug levels. DESIGN/METHODS: In this double-blind, phase 3 study (PREVAIL; NCT01142193), patients taking 1-3 concomitant AEDs were randomized to placebo (n=125) or USL255 (n=124), titrated over 3 weeks (50 mg/week), and maintained at 200 mg/day for 8 weeks. Incidence of spontaneously-reported TEAEs was assessed by study phase and severity. Neurocognitive adverse events were also summarized. RESULTS: Overall, the incidence of TEAEs was 66% with USL255 and 50% with placebo treatment (P=.015), and the majority were mild-to-moderate in intensity. A higher proportion of patients reported TEAE onset during the 3-week titration phase than during the first or last 4 weeks of the maintenance phase. Somnolence, dizziness, paraesthesia, weight decrease, fatigue, and headache were the most commonly reported TEAEs. The proportion of patients reporting a neurocognitive/neuropsychiatric TEAE (eg, memory impairment, psychomotor slowing) was less than 3% in both treatment groups, with the exception of disturbance in attention (2.4% [USL255]; 3.2% [placebo]). A majority of these events resolved before completion of maintenance. No deaths were reported and none of the serious TEAEs with USL255 were considered treatment related (USL255, 1.6%; placebo, 1.6%). CONCLUSIONS: USL255 demonstrated a favorable adverse event profile in patients with refractory POS with low incidence of neurocognitive adverse events, suggesting USL255 may provide a significant benefit to patients with epilepsy. Study Supported by: Upsher-Smith Laboratories, Inc.

OBJECTIVE: Evaluate efficacy, safety, and impact on quality of life (QoL) of adjunctive treatment with USL255, once-daily extended-release (XR) topiramate, in adults with refractory partial-onset seizures (POS). BACKGROUND: Treatment nonadherence, common in patients with epilepsy, can increase seizures and adversely affect QoL. Compared with immediate-release (IR) antiepileptic drugs (AEDs), XR formulations can improve adherence by reducing dosing frequency and may decrease treatment-emergent adverse events (TEAEs) caused by peak-dose toxicity. At the same daily dose, USL255 is pharmacokinetically equivalent to IR topiramate and reduces plasma fluctuations. DESIGN/METHODS: In this double-blind, phase 3 study (PREVAIL; NCT01142193), patients taking 1-3 concomitant AEDs were randomized to placebo (n=125) or USL255 (n=124), titrated over 3 weeks (50 mg/week), and maintained at 200 mg/day for 8 weeks. Primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and 50% responder rate following 11 weeks of treatment. Safety (TEAEs, laboratory findings, physical/neurological exams) and treatment effects on the Quality of Life in Epilepsy - Problems (QOLIE-31-P) and Clinical Global Impression-Change (CGI-C) scale were evaluated. RESULTS: USL255 resulted in greater reduction in POS frequency (39.5% vs 21.6%, P<.001) and greater 50% responder rate (37.9% vs 23.2%, P=.013) vs placebo. TEAE incidence was 66% (USL255) and 50% (placebo) (P=.015). Less than 3% of USL255-treated patients reported individual neurocognitive or neuropsychiatric TEAEs. No serious AEs (1.6% each group) were deemed USL255 related, and there were no abnormal trends in safety evaluations. The QOLIE-31-P seizure-worry subscale was significantly improved (14.1 vs 4.1, P<.001) with USL255 vs placebo, though the overall score was not significantly different (5.2 vs 4.5). Almost twice as many USL255-treated patients had improved CGI-C scores (37.8% vs 19.4%; P<.002). CONCLUSIONS: The PREVAIL study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control, was well tolerated with few neurocognitive/neuropsychiatric side effects, and may functionally benefit patients with epilepsy. Study Supported by: Upsher-Smith Laboratories, Inc.

OBJECTIVE: Evaluate early efficacy and timing of treatment-emergent adverse events (TEAEs) with USL255, a once-daily extended-release topiramate formulation. BACKGROUND: Since many antiepileptic drugs require titration to achieve effective doses, it may be helpful to understand how quickly patients may experience symptom improvement after starting treatment. DESIGN/METHODS: In this double-blind, phase 3 study (PREVAIL; NCT01142193), participants with partial-onset seizures (POS) on 1-3 concomitant AEDs were randomized to placebo (n=125) or USL255 (n=124), titrated over 3 weeks (50 mg/week), and maintained at 200 mg/day for 8 weeks. Efficacy endpoints included median percent reduction from baseline in weekly POS frequency and 50% responder rate during titration and maintenance phases separately. Post-hoc analyses included weekly seizure reduction and TEAEs by phase. RESULTS: During titration, USL255 was associated with significant reductions in weekly POS frequency vs placebo (34% vs 8.6%; P<.001), which continued through maintenance (46% vs 22%; P=.001). During titration, 50% responder rate was significantly greater following USL255 treatment (34% vs 18%; P=.007); similar results were observed during maintenance (44% vs 31%; P=.048). When evaluated weekly, POS frequency was significantly reduced as early as Week 1 with USL255 (29% vs 9.2%; P<.05). Incidence of TEAEs was highest during titration for both USL255 (50%) and placebo (31%). After the first 4 weeks of maintenance, there was a 2% difference in TEAE incidence between USL255 (26%) and placebo (24%). Similar results were seen for nervous system disorder TEAEs, including neurocognitive and neuropsychiatric events, most of which resolved during maintenance. CONCLUSIONS: USL255 demonstrated significant efficacy as early as the first week of treatment (50 mg/day), with sustained benefit throughout the study. Incidence of TEAEs was higher in the titration than maintenance phase. USL255 demonstrated an early onset of efficacy, with TEAE rates similar to placebo after 4 weeks of maintenance treatment. Study Supported by: Upsher-Smith Laboratories, Inc.

SummaryObjectiveTo evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended‐release capsules, as an adjunctive treatment for refractory partial‐onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs.MethodsIn this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once‐daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE‐31‐P) and clinical global impression of change (CGI‐C), were evaluated.ResultsAcross the entire 11‐week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life.SignificanceThe PREVAIL phase III clinical study demonstrated that once‐daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects.

OBJECTIVE: This prospective non-interventional study (NCT01098162) evaluated seizure control and tolerability of lacosamide in adults with partial-onset seizures receiving one antiepileptic drug (AED). BACKGROUND: Approval of lacosamide (up to 400mg/day) as adjunctive treatment of partial-onset seizures in adults was based on data from studies in treatment-resistant patients treated with up to three concomitant AEDs. DESIGN/METHODS: This 6-month study, conducted in clinical practice in Germany, was planned to enroll 500 evaluable patients. The current interim analysis reports data from 329 patients evaluable for seizure control and 367 patients evaluable for safety. Background AED monotherapy was based on the independent decision of the treating physician. Outcome variables included reduction in seizure frequency (蠅50% and 蠅75%), seizure freedom, and Clinical Global Impression of Change (CGIC) at last study visit (6 months) compared with 3-month retrospective baseline, as well as treatment-emergent adverse events (TEAEs). RESULTS: At the last visit, 40.7% were free from seizures for 蠅3 months (median lacosamide dose: 200mg/day [50-600mg/day]). 70.2% of patients showed a 蠅50% reduction and 59.9% showed a 蠅75% reduction in seizure frequency (during last 3 months of study). On the CGIC, physicians judged symptoms as "very much improved" in 26.5% or "much improved" in 36.9% of patients. Reduction in seizure frequency was greater for patients aged 蠅65 years (蠅50% responders 78.2%, seizure freedom 54.5%, n=55) vs <65 years; patients with epilepsy duration ≤5 years (蠅50% responders 75.4%, seizure freedom 48.5%, n=130) vs >5 years; and patients who received lacosamide as first adjunctive treatment (蠅50% responders 81.3%, seizure freedom 55.4%, n=112) vs history of more AEDs. 12.5% of patients discontinued due to a TEAE. The most common TEAEs judged by physicians to be related to lacosamide were fatigue (10.1%, n=37), dizziness (8.7%, n=32), headache and nausea (2.2%, n=8 each). CONCLUSIONS: This interim analysis indicates improved seizure control, generally well tolerated when lacosamide was used as adjunctive treatment to AED monotherapy in routine clinical practice. Study Supported by: UCB Pharma