Abstracts

Rationale: In the absence of head-to-head clinical trials among antiepileptic drugs (AEDs) for patients with refractory partial-onset seizures (POS), comparative analyses have only investigated treatment efficacy relative to placebo. Thus, the objectives are to (1) perform a systematic literature review of the pivotal trials used for US FDA approval of each AED for refractory POS and (2) compare the efficacies of each approved AEDs using indirect comparison methods.Methods: A systematic literature review was conducted to identify the pivotal trials that served as the basis for FDA approval of each AED for refractory POS, including complex partial seizures (CPS). The search adhered to standard processes described in the Cochrane Handbook for Systematic Reviews of Interventions.1 Trials that met the following criteria were included: (1) phase III randomized, double-blind, placebo-controlled, parallel-group design, with an 8–14 week maintenance period; (2) enrolled patients age ≥16 years with refractory POS, including CPS; and (3) patients received either placebo or an AED approved for POS after 1996. The odds ratio (OR) for 50% responders among AED and placebo for each study was calculated. The ORs were pooled by dosage for each AED using DerSimonian and Laird random-effects analysis.2Results: A total of 39 publications describing pivotal results for 15 AEDs were identified. Five studies reporting data for unapproved dosages and 4 that did not meet the maintenance period requirement were excluded, resulting in 30 publications with data for 12 AEDs. Figure 1 illustrates a forest plot of the OR of the 50% responder rate for pooled dosages by AED. Among all AEDs identified, tiagabine (56 mg/day), pregabalin (600 mg/day), and vigabatrin (3000 mg/day) increased the odds of responding fourfold vs placebo. The odds of achieving seizure freedom were >7 times in patients receiving vigabatrin (3000 mg/day) and levetiracetam (3000 mg/day) vs placebo (Figure 2).Conclusions: The analysis is limited to the published literature and does not capture long-term adverse effects or other AED characteristics that may influence treatment choice. Despite this limitation, our analyses showed that GABA-ergic AEDs were effective in the treatment of refractory POS; however, these agents are used less frequently than other medications included in this comparison. Funded by Lundbeck LLC 1Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. 2008. Wiley Online Library. Available at http://handbook.cockrane.org/ Updated March 2011. 2DerSimonian R., Laird N. Controlled Clinical Trials. 1986;7(3):177–88.