Abstracts

Rationale:
Levetiracetam (LEV) is an antiepileptic drug (AED) which has broad-spectrum efficacy with favorable pharmacokinetic and safety profiles. Following the approval for use as adjunctive therapy for primary generalized tonic-clonic seizures (PGTCS) in patients aged ≥4 years in Japan, the post-marketing surveillance was conducted between June 2016 and May 2019 to further evaluate the safety and efficacy of LEV as adjunctive therapy for Japanese patients with PGTCS in clinical practice (EP0082).
Method:
Eligible patients were adults (≥16 years) and children (4-15 years) who had uncontrolled PGTCS despite treatment with other AEDs. LEV was administered orally according to the dosage specified in the package insert for tablets and dry syrup. The observation period was 28 weeks. The safety outcomes included treatment-emergent adverse event (TEAEs), adverse drug reactions (ADRs) and the specific ADRs predefined as important safety concerns. The efficacy outcomes included: the global improvement scale (GIS) in which the investigator rated the overall change in each patient’s symptoms at the end of treatment as “markedly improved”, “improved”, “unchanged” or “Aggravation”; and the percentage reduction in PGTCS frequency per 4 weeks from baseline to post-treatment.
Results:
A total of 506 patients were enrolled into the study, and 365 (267 adults and 98 children) were included in the safety analysis. Approximately two-thirds of patients were pretreated with sodium valproate (Table 1). Seventy-five patients (20.55%) discontinued LEV (TEAEs: n=33 [9.04%], lack of efficacy: n=19 [5.21%]). Sixty-five patients (17.81%) reported at least one ADR (Table 2). The most common ADRs were somnolence (6.85%), irritability (1.92%), agitation (1.64%), and dizziness (1.10%). The proportion of patients who reported ADRs was similar between adults (16.85%) and children (20.41%). Serious ADRs occurred in 6 patients (1.64%). For the specific ADRs, aggression occurred in 13 patients (6 adults [2.25%] and 7 children [7.14%]) and hepatic failure–hepatitis occurred in 1 patient (adult). Of these, 1 child had aggression classified as serious. Other specific ADRs were classified as non-serious. In the efficacy assessment, 313 were included in analysis of the GIS and the symptom change in 199 patients (63.58%) was rated as “markedly improved” or “improved.” The median percentage reduction in PGTCS frequency was 100.00% (interquartile range, 50.00% to 100.00%). Both the efficacy outcomes were similar between adults and children.
Conclusion:
The safety profile of LEV as adjunctive therapy to other AEDs in Japanese patients with uncontrolled PGTCS in clinical practice was similar to that filed in the new drug application. No ADRs indicating new safety concerns were observed during the observation period of 28 weeks. Its efficacy profile was also favorable, which was supported by the analysis of the GIS and percentage reduction in PGTCS seizure frequency.
Funding:
:UCB Pharma-sponsored.