Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial

Baulac, Michel; Rosenow, Felix; Toledo, Manuel; Terada, Kiyohito; Li, Ting; Backer, Marc De; Werhahn, Konrad J.; Brock, Melissa

doi:10.1016/s1474-4422(16)30292-7

Cited by 141 publications

(143 citation statements)

References 32 publications

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“…Notably, in this study, seizure freedom rates were calculated using the full FAS not just patients completing treatment. These results are consistent with those from SP993, where 73.6% of newly diagnosed epilepsy patients treated with lacosamide monotherapy completed 6 months’ and 59.5% completed 12 months’ treatment without seizures 7. Smaller studies have also shown comparable seizure freedom rates 10, 11.…”

Section: Discussionsupporting

confidence: 88%

“…Its efficacy as monotherapy in patients with focal seizures has been demonstrated in two double‐blind randomized trials; a head‐to‐head non‐inferiority trial of lacosamide vs the continuous‐release (CR) formulation of carbamazepine used for EU approval (SP993)7; and a historical‐controlled, conversion to monotherapy trial (SP902) for US approval 8. In the SP993 non‐inferiority trial in patients with newly diagnosed epilepsy, 73.6% of lacosamide‐treated and 69.7% of carbamazepine‐CR‐treated patients (Full Analysis Set) completed 6 months on last evaluated dose without a seizure.…”

Section: Introductionmentioning

confidence: 99%

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Lacosamide monotherapy in clinical practice: A retrospective chart review

et al. 2018

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ObjectiveTo assess effectiveness and tolerability of first‐line and conversion to lacosamide monotherapy for focal seizures.Materials and MethodsRetrospective, non‐interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs).ResultsA total of 439 patients were included (98 first‐line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first‐line and 103 conversion to monotherapy]). First‐line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%‐70.0%) and 62.5% (213/341; 57.1%‐67.6%), respectively. Kaplan‐Meier estimates of 12‐month retention rates were 81.2% and 91.4% for first‐line and conversion to monotherapy, respectively. First‐line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%‐78.9%) and 68.9% (59.1%‐77.7%), respectively. At OP2, 66.3% of first‐line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first‐line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first‐line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%).ConclusionsLacosamide was effective and well tolerated as first‐line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizures.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Lacosamide monotherapy in clinical practice: A retrospective chart review

et al. 2018

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“…After excluding duplicates (1213) and reading title and abstracts, 14 RCTs were initially considered. 17,19 The following comparisons were included in the RCTs: phenytoin (PHT) vs valproic acid (VPA), 13 carbamazepine-immediate release (CBZ-IR) vs lamotrigine (LTG) vs gabapentin (GBP), 14 carbamazepine-controlled release (CBZ-CR) vs LTG vs levetiracetam (LEV), 15 LEV vs VPA and LEV vs CBZ-CR, 16 and CBZ-CR vs lacosamide (LCM). Hence, five RCTs were included (Figure 1), which recruited 1425 patients with newly diagnosed epilepsy.…”

Section: Resultsmentioning

confidence: 99%

Antiepileptic drug monotherapy for epilepsy in the elderly: A systematic review and network meta‐analysis

et al. 2019

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Objective: To estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in the elderly with new-onset epilepsy. Methods: We searched electronic databases for randomized controlled trials (RCTs) of monotherapy AEDs to treat epilepsy in elderly. The following outcomes were analyzed: seizure freedom and withdrawal from the study for any cause at 6 and 12 months; withdrawal from the study for any adverse event (AE) at 12 months; and occurrence of any AE at 12 months. Effect sizes were estimated by network metaanalyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA) and mean ranks. Results: Five RCTs (1425 patients) were included. Included AEDs were carbamazepine immediate-and controlled-release (CBZ-IR, CBZ-CR), gabapentin (GBP), lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), phenytoin (PHT), and valproic acid (VPA). At the pairwise and network meta-analyses, there were no differences in any of the comparison according to 6-and 12-month seizure freedom.The treatment with CBZ-IR and CBZ-CR was associated with a higher risk of withdrawal than LTG, LEV, or VPA, and CBZ-IR had the overall highest probability of discontinuation across all AEDs. According to SUCRA, the following had the greatest likelihood ranking best for seizure freedom at 6 and 12 months: LCM, LTG, and LEV. CBZ-CR and CBZ-IR had the highest probabilities of being worst for the 12-month retention. CBZ-IR, CBZ-CR, and GBP had the highest probabilities of withdrawal from the study for AEs, , and VPA had the highest probability of being the best-tolerated option. Significance: Although no significant difference in efficacy was found across treatments, LCM, LTG, and LEV had the highest probability of ranking best for achieving seizure freedom. CBZ-IR and CBZ-CR showed a poor tolerability profile, leading to higher withdrawal rates compared to LEV and VPA. K E Y W O R D Selderly, epilepsy, monotherapy, network meta-analysis, randomized-controlled trials 2246 | LATTANZI eT AL.

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“…Four trials [17][18][19][20] were included in the review, all of which were included in the meta-analysis ( Figure 1). Four trials [17][18][19][20] were included in the review, all of which were included in the meta-analysis ( Figure 1).…”

Section: Results Of the Searchmentioning

confidence: 99%

“…[17][18][19] Details of the included studies and participants are given in Tables 1 and Table S1, respectively. The studies included 2856 participants according to the ITT, 1445 for CBZ-CR and 1411 for the comparative AEDs.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis

Lattanzi

Zaccara²,

Giovannelli

et al. 2018

Acta Neurol Scand

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Second and third generation AEDs have been directly compared to controlled-release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal epilepsy. Conversely, no head-to-head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta-analysis (NMA). Randomized, double-blinded, parallel group, monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed untreated epilepsy with focal-onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12 months, the occurrence of treatment-emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6- and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659, 95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ-CR.

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Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial

Cited by 141 publications

References 32 publications

Lacosamide monotherapy in clinical practice: A retrospective chart review

Lacosamide monotherapy in clinical practice: A retrospective chart review

Antiepileptic drug monotherapy for epilepsy in the elderly: A systematic review and network meta‐analysis

Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis

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