Abstracts

Rationale: It is not feasible to make direct comparisons between treatments for Lennox-Gastaut Syndrome (LGS) without head-to-head studies. Therefore, we performed an indirect comparison of the relative efficacies of clobazam, felbamate, lamotrigine, topiramate, and rufinamide as adjunctive treatments for patients with LGS.Methods: We compared results from a Phase III clobazam study in LGS¹ with results from randomized controlled trials of approved adjunctive LGS therapies from a 2009 Cochrane Review.² One of two lamotrigine studies in the Cochrane Review was not included in our analysis since the randomization methodology for the published study was unclear. Since all 5 studies in our present analysis, including the clobazam trial, employed these drugs with adjunctive therapy vs. placebo plus adjunctive therapy, we employed traditional, pair-wise indirect comparison techniques to evaluate clobazam vs. the drugs approved for LGS. As trial outcomes were not identical, we transformed the primary endpoint of each study into effect size (using Cohen s d) to conduct indirect comparisons. Typical interpretations of Cohen s d results are: d<0.2, change not detectable; 0.2?d<0.5, small change; 0.5?d<0.8, moderate change; and 0.8?d, large change.Results: High-dosage clobazam (1.0 mg/kg/day) had the greatest effect size, followed by medium-dosage clobazam (0.5 mg/kg/day), and rufinamide (figure below). According to Cohen s d interpretation, effect size (0.80) for high-dosage CLB was important. Medium-dosage clobazam and rufinamide had d-values >0.50, indicating a moderate clinical effect vs. placebo. Indirect comparisons of numbers of total seizures and drop or tonic-clonic seizures also supported the greater effect of high-dosage clobazam. Because of the low number of studies in the analysis, however, no results achieved statistical significance.Conclusions: Based on indirect comparisons, high- and medium-dosage clobazam was estimated to be more efficacious than other LGS treatments evaluated. Our analysis relied on published data and did not have the advantages of direct head-to-head comparison of clobazam with other alternatives. Further comparative research is ongoing to assess the usefulness of clobazam for LGS. References: ¹Conry J, et al. Epilepsia. 2010;Abstract #1.283. ²Hancock EC, et al. Cochrane Database Syst Rev. 2009;8:CD003277.