Dataset Information

A noninterventional study evaluating the effectiveness and safety of lacosamide added to monotherapy in patients with epilepsy with partial-onset seizures in daily clinical practice: The VITOBA study.

ABSTRACT:

Objective

Evidence 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.

Methods

We 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.

Results

Five 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.

Significance

These 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.

SUBMITTER: Runge U

PROVIDER: S-EPMC4737283 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Publications

A noninterventional study evaluating the effectiveness and safety of lacosamide added to monotherapy in patients with epilepsy with partial-onset seizures in daily clinical practice: The VITOBA study.

Runge Uwe U Arnold Stephan S Brandt Christian C Reinhardt Fritjof F Kühn Frank F Isensee Kathleen K Ramirez Francisco F Dedeken Peter P Lauterbach Thomas T Noack-Rink Matthias M Mayer Thomas T

Epilepsia 20151103 12

<h4>Objective</h4>Evidence 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.<h4>Methods</h4>We conducted a 6-month obser ...[more]

PMID: 26526971

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Project description:Background. The relative efficacy and safety of lacosamide as adjunctive therapy compared to other antiepileptic drugs has not been well established. Objective. To determine if lacosamide provides improved efficacy and safety, reduced length of hospital stay and improved quality of life compared with other anti-epileptic therapies for adults with partial-onset seizures. Data Sources. A systematic review of the medical literature using Medline (1946-Week 4, 2012), EMBASE (1980-Week 3, 2012), Cochrane Central Register of Controlled Trials (Issue 1 of 12, January 2012). Additional studies were identified (through to February 7, 2012) by searching bibliographies, the FDA drug approval files, clinical trial registries and major national and international neurology meeting abstracts. No restrictions on publication status or language were applied. Study Selection. Randomized controlled trials of lacosamide in adults with partial-onset seizures were included. Data Extraction. Study selection, extraction and risk of bias assessment were performed independently by two authors. Authors of studies were contacted for missing data. Data Synthesis. All pooled analyses used the random effects model. Results. Three trials (1311 patients) met inclusion criteria. Lacosamide increased the 50% responder rate compared to placebo (RR 1.68 [95% CI 1.36 to 2.08]; I(2) = 0%). Discontinuation due to adverse events was statistically significantly higher in the lacosamide arm (RR3.13 [95% CI 1.94 to 5.06]; I(2) = 0%). Individual adverse events (ataxia, dizziness, fatigue, and nausea) were also significantly higher in the lacosamide group. Limitations. All dosage arms from the included studies were pooled to make a single pair-wise comparison to placebo. Selective reporting of outcomes was found in all of the included RCTs. Conclusions. Lacosamide as adjunctive therapy in patients with partial-onset seizures increases the 50% responder rate but with significantly more adverse events compared to the placebo.

Project description:ObjectiveTo evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy.MethodsThis historical-controlled, double-blind study (NCT00520741) enrolled patients aged 16-70 years on stable doses of 1-2 antiepileptic drugs (AEDs) and experiencing 2-40 partial-onset seizures per 28 days during the 8-week prospective Baseline. Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day and titrated over 3 weeks to randomized dose. Patients then withdrew background AEDs over 6 weeks and entered a 10-week Monotherapy Phase. The primary assessment was the Kaplan-Meier-predicted percentage of patients on 400 mg/day in the full analysis set (FAS) meeting ≥ 1 predefined seizure-related exit criterion by day 112, compared with the historical-control threshold (65.3%).ResultsFour hundred twenty-five patients were enrolled and were eligible for safety analyses (400 mg/day, n = 319; 300 mg/day, n = 106). A total of 271 (63.8%) of 425 patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and Monotherapy Phases). Among 284 patients in the 400 mg/day group in the FAS, 82 (28.9%) met ≥ 1 exit criterion; the Kaplan-Meier-predicted exit percentage at day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6-35.5%) was lower than the historical control. When exit events, withdrawal due to treatment-emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8-37.8%) was also lower than the historical control. Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change (75.4%) and Patient Global Impression of Change (74.3%). Overall, the most common (>10%) TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild-to-moderate in intensity. Seventy-two patients (16.9%) discontinued due to TEAEs. Seventeen patients (4%, all receiving 400 mg/day) experienced serious AEs.SignificanceLacosamide 400 mg/day monotherapy was effective, with a favorable safety profile in patients with focal epilepsy.

Project description:ObjectiveTo evaluate the effectiveness and tolerability of lacosamide added to one or two antiepileptic drugs (AEDs) in the treatment of patients with brain tumor-related epilepsy (BTRE), and to evaluate patients' global impression of change and quality of life (QoL).MethodsThis was a prospective, multicenter, single-arm, noninterventional study with a 6-month observation period (EP0045; NCT02276053). Eligible patients (≥16 years old) had active BTRE secondary to low-grade glioma (World Health Organization grade 1 and 2) and were receiving treatment with one or two AEDs at baseline. Lacosamide was initiated by the treating physician in the course of routine clinical practice. Primary outcomes were 50% responders (≥50% reduction in focal seizure frequency from baseline) and Patient's Global Impression of Change (PGIC) at month 6. Secondary outcomes included seizure-free status and Clinical Global Impression of Change (CGIC) at month 6, change in QoL (5-Level EuroQol-5 Dimension Quality of Life Assessment) and symptom outcomes (MD Anderson Symptom Inventory-Brain Tumor) from baseline to month 6, and Kaplan-Meier estimated 6-month retention on lacosamide. Safety variables included adverse drug reactions (ADRs).ResultsPatients were recruited from 24 sites in Europe. Ninety-three patients received lacosamide (mean [standard deviation] age = 44.5 [14.7] years; 50 [53.8%] male; median baseline focal seizure frequency = five seizures/28 days [range = 1-280]), of whom 79 (84.9%) completed the study. At 6 months, 66 of 86 (76.7%) patients were 50% responders and 30 of 86 (34.9%) were seizure-free. Improvements on PGIC were reported by 49 of 76 (64.5%) patients. Based on CGIC, 52 of 81 (64.2%) patients improved. QoL and symptoms outcome measures remained stable. Kaplan-Meier estimated 6-month retention rate was 86.0% (N = 93). Fifteen (16.1%) patients reported ADRs; four (4.3%) had ADRs leading to discontinuation (N = 93).SignificanceResults of this prospective, noninterventional study suggest that add-on lacosamide is effective and generally well tolerated in patients with BTRE.

Project description:ObjectiveA large-scale, double-blind trial (SP0993; NCT01243177) demonstrated that lacosamide was noninferior to controlled-release carbamazepine (carbamazepine-CR) in terms of efficacy, and well tolerated as first-line monotherapy in patients (≥16 years of age) with newly diagnosed epilepsy. We report primary safety outcomes from the double-blind extension of the noninferiority trial (SP0994; NCT01465997) and post hoc analyses of pooled long-term safety and efficacy data from both trials.MethodsPatients were randomized 1:1 to lacosamide or carbamazepine-CR. Doses were escalated (lacosamide: 200/400/600 mg/d; carbamazepine-CR: 400/800/1200 mg/d) based on seizure control. Eligible patients continued randomized treatment in the extension. Primary outcomes of the extension were treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Post hoc analyses of data from combined trials included 12- and 24-month seizure freedom and TEAEs by number of comorbid conditions.ResultsA total of 886 patients were treated in the initial trial and 548 in the extension; 211 of 279 patients (75.6%) on lacosamide and 180/269 (66.9%) on carbamazepine-CR completed the extension. In the extension, 181 patients (64.9%) on lacosamide and 182 (67.7%) on carbamazepine-CR reported TEAEs; in both groups, nasopharyngitis, headache, and dizziness were most common. Serious TEAEs were reported by 32 patients (11.5%) on lacosamide and 22 (8.2%) on carbamazepine-CR; 12 (4.3%) and 21 (7.8%) discontinued due to TEAEs. In the combined trials (median exposure: lacosamide 630 days; carbamazepine-CR 589 days), Kaplan-Meier estimated proportions of patients with 12- and 24-month seizure freedom from first dose were 50.8% (95% confidence interval 46.2%-55.4%) and 47.0% (42.2%-51.7%) on lacosamide, and 54.9% (50.3%-59.6%) and 50.9% (46.0%-55.7%) on carbamazepine-CR. Incidences of drug-related TEAEs and discontinuations due to TEAEs increased by number of comorbid conditions and were lower in patients on lacosamide.SignificanceLong-term (median ~2 years) lacosamide monotherapy was efficacious and generally well tolerated in adults with newly diagnosed epilepsy. Seizure freedom rates were similar with lacosamide and carbamazepine-CR.

Dataset Information

A noninterventional study evaluating the effectiveness and safety of lacosamide added to monotherapy in patients with epilepsy with partial-onset seizures in daily clinical practice: The VITOBA study.

Objective

Methods

Results

Significance

Publications

A noninterventional study evaluating the effectiveness and safety of lacosamide added to monotherapy in patients with epilepsy with partial-onset seizures in daily clinical practice: The VITOBA study.

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