Objective: We conducted indirect comparisons of the relative efficacies of clobazam, felbamate, lamotrigine, topiramate, and rufinamide as adjunctive treatments for patients with Lennox-Gastaut syndrome (LGS).
Background It is not feasible to make direct comparisons of treatments for LGS without head-to-head studies.
Design/Methods: We compared Phase III clobazam results in LGS1 with RCT results of approved adjunctive LGS therapies from a 2009 Cochrane Review.2 One of two lamotrigine studies in the Cochrane Review was not included, since randomization methodology for the published study was unclear. Since all 5 studies in our analysis, including the clobazam trial, employed these drugs with adjunctive therapy vs. placebo plus adjunctive therapy, we used traditional, pair-wise indirect comparisons to evaluate clobazam vs. the other drugs. As trial outcomes were not identical, we transformed primary endpoints into effect sizes (using Cohen’s d). 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. According to Cohen's d interpretation, effect size (0.80) for high-dosage clobazam was important. Medium-dosage clobazam and rufinamide had d-values >0.50, indicating a moderate clinical effect vs. placebo. Comparisons of numbers of total and drop or tonic-clonic seizures also supported the greater effect of high-dosage clobazam. Because of the few studies in the analysis, however, no results achieved statistical significance.
Conclusions: High- and medium-dosage clobazam was estimated to be more efficacious than other LGS treatments. Our analysis relied on published data and could not draw on direct head-to-head data of clobazam with alternatives. Further comparative research is ongoing to assess the usefulness of clobazam for LGS.1Ng