Long‐term safety and efficacy of lacosamide and controlled‐release carbamazepine monotherapy in patients with newly diagnosed epilepsy

Abstract

Objective: A 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. Methods: Patients 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. Results: A 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.This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Long‐term safety and tolerability of lacosamide monotherapy in patients with epilepsy: Results from a multicenter, open‐label trial

“…The overall percentage of patients reporting any TEAEs during the treatment period in SP1042 was lower in this open‐label trial (57.5%) versus the double‐blind (SP0993; 74%) 2 and double‐blind extension (SP0994; 64.9%) 8 trials. In this trial, 0.9% of patients discontinued due to TEAEs and 13.2% of patients reported serious TEAEs, which is lower or slightly higher, respectively, to rates observed in the double‐blind trials 2,8 .…”

“…The overall percentage of patients reporting any TEAEs during the treatment period in SP1042 was lower in this open‐label trial (57.5%) versus the double‐blind (SP0993; 74%) 2 and double‐blind extension (SP0994; 64.9%) 8 trials. In this trial, 0.9% of patients discontinued due to TEAEs and 13.2% of patients reported serious TEAEs, which is lower or slightly higher, respectively, to rates observed in the double‐blind trials 2,8 . This may reflect an enriched population in the open‐label trial because patients who did not respond to lacosamide in the double‐blind trials, or who reported TEAEs leading to discontinuation, were not enrolled.…”

“…4,5 Results of a large-scale, double-blind trial (SP0993; NCT01243177) 2 demonstrated that lacosamide was well tolerated as first-line monotherapy in patients ≥16 years with recently or newly diagnosed focal (partial-onset) seizures (simple partial, complex partial, or partial evolving to secondarily generalized with clear focal origin) or generalized tonic-clonic seizures (without clear focal origin), and was noninferior to controlled-release carbamazepine. The results of a double-blind extension of SP0993 (SP0994 [NCT01465997] 8 ; with the same target lacosamide doses as SP0993 of 200, 400, and 600 mg/day), and post hoc analyses of pooled long-term efficacy and safety data from SP0993 and SP0994, showed that treatment with lacosamide monotherapy was well tolerated and efficacy was maintained over a median of approximately two years' treatment. 8 Open-label, follow-up trials provide valuable information regarding the long-term tolerability and efficacy of ASMs.…”

How Can an Na+ Channel Inhibitor Ameliorate Seizures in Lennox–Gastaut Syndrome?

“…Lacosamide therefore could potentially have a narrower scope of antiseizure action, with less interference on normal bursts (especially those similar to seizure discharges, such as the repetitive rebound bursts in the cerebellar nuclear neurons triggered by the input from Purkinje neurons) 58 . This may partly explain why there is less ataxia and fewer relevant adverse events associated with lacosamide in clinical settings 59 . In‐depth considerations based on the molecular actions and therapeutic responses of ASDs are always advisable, and may in turn contribute to more pathophysiological understanding and a successful therapeutic regimen for each individual patient.…”

Lacosamide add-on treatment in refractory focal epilepsy: experience of a single tertiary center

“…Hem etiyoloji; hem de LCM eklenme sırası ile ilgili olarak elde ettiğimiz bulgular literatür ile uyumlu görünmektedir. [17,11] Randomize kontrollü çalışmalarda LCM ile yan etki görülme sıklığı %37-43.3 arasında yayınlanmış; [15,21,22] azalan sıklıkta dizziness (sersemlik), uyku hali, çift görme, başağrısı ve kusma bildirilmiştir. [23] Bununla birlikte yan etki görülme oranlarının; idame fazında, titrasyon fazına kıyasla belirgin şekilde düştüğü de kaydedilmiştir.…”