title: Levetiracetam extended release and levetiracetam immediate release as adjunctive treatment for partial-onset seizures: an indirect comparison of treatment-emergent adverse events using meta-analytic techniques.
abstract: The safety profiles of once-daily adjunctive levetiracetam (LEV) extended release (XR) (1000mg/day) and adjunctive LEV immediate release (IR) (500mg twice daily) were compared using data from three randomized, placebo (PBO)-controlled phase III clinical trials in patients with partial-onset seizures. MedDRA 9.0 treatment-emergent adverse events (TEAEs) were indirectly compared using meta-analytic techniques, including calculation of risk difference (RD) and mixed-effects analysis. Statistical significance was set at 10% alpha risk, the normative value for these analyses. Data from 555 patients older than 16 (204 LEV IR, 70 LEV XR, 281 PBO) were analyzed. Following adjustment for incidence of placebo TEAEs, LEV XR showed statistically significantly lower rates of TEAEs than LEV IR across nervous system disorders (RD=-18%, P=0.03), psychiatric disorders (RD=-11%, P=0.08), and metabolism and nutrition disorders (RD=-3%, P=0.08). Among nervous system disorders, the RD for headache favored LEV XR (RD=-11%, P=0.08). These results suggest that adjunctive LEV XR may be associated with a lower incidence of nervous system, psychiatric, and nutritional and metabolic TEAEs as compared with LEV IR. However, this difference was observed at a broad scale and not at a specific TEAE level except for headache.
authors.affiliation: G3P Epidemiology, UCB Pharma S.A., Brussels, Belgium. florent.richy@ucb.com
authors.forename: Florent F
authors.initials: FF
authors.lastname: Richy
authors.forename: Soutrik
authors.initials: S
authors.lastname: Banerjee
authors.forename: Yves
authors.initials: Y
authors.lastname: Brabant
authors.forename: Sandra
authors.initials: S
authors.lastname: Helmers
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000379:methods; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam