A cross-national cost-effectiveness analysis of brivaracetam focusing on psychiatric and behavioral adverse effects

Levetiracetam (LEV) has been widely used as an antiseizure medication (ASM), but is associated with psychiatric and behavioral adverse effects (PBAEs). Brivaracetam (BRV) has demonstrated better psychiatric tolerability, albeit at a higher cost. This study aimed to evaluate the cost-effectiveness of initiating BRV versus LEV therapy with a subsequent switch to BRV in the event of PBAEs across the US, Australia, and Japan.

We developed a decision tree model with a 10-year time horizon comparing two strategies across the US, Australia, and Japan: initial BRV therapy versus initial LEV therapy with a switch to BRV upon the occurrence of PBAEs. We utilized clinical trial data and regional cost estimates to conduct base-case and probabilistic sensitivity analyses.

The results of the base-case analyses indicated that initial BRV therapy was cost-effective only in Australia. The results of the sensitivity analyses revealed that the probability of initial BRV being cost-effective was 0% in the US, 49.6% in Japan, and 99.99% in Australia. In Japan, when the risk of LEV-induced PBAEs was assumed to be 24%, the probability that initial BRV therapy would be cost-effective rose to 70%, supporting the potential utility of an initial BRV strategy in high-risk populations. By contrast, in the US, the risk of PBAEs needed to exceed 76% to achieve a comparable cost-effectiveness probability.

While the initial BRV strategy consistently demonstrated cost-effectiveness in Australia, it failed to do so in Japan and the US. However, Japan presents a unique opportunity where BRV can be used cost-effectively when combined with pre-assessments of LEV-induced risk for PBAEs.

BRV causes fewer PBAEs than LEV, but costs more, creating a clinical dilemma. A cost-effectiveness analysis comparing BRV versus LEV as initial monotherapy with a focus on PBAEs was conducted across the US, Australia, and Japan. The results indicated that compared with LEV, BRV is cost-effective in Australia, but not in the US. In Japan, BRV is cost-effective as initial treatment only for patients at high risk for LEV-induced PBAEs.