Meta-analysis and cost-effectiveness of second-line antiepileptic drugs for status epilepticus

Objective Compare the cost and effectiveness of nonbenzodiazepine antiepileptic drugs (non-BZD AEDs) for treatment of BZD-resistant convulsive status epilepticus (SE). Methods Decision analysis model populated with effectiveness data from a systematic review and metaanalysis of the literature, and cost data from publicly available prices. The primary outcome was cost per seizure stopped ($/SS). Sensitivity analyses evaluated the robustness of the results across a wide variation of the input parameters. Results We included 24 studies with 1,185 SE episodes. The most effective non-BZD AED was phenobarbital (PB) with a probability of SS of 0.8 (95% confidence interval [CI]: 0.69-0.88), followed by valproate (VPA) (0.71 [95% CI: 0.61-0.79]), lacosamide (0.66 [95% CI: 0.51-0.79]), levetiracetam (LEV) (0.62 [95% CI: 0.5-0.73]), and phenytoin/fosphenytoin (PHT) (0.53 [95% CI: 0.39-0.67]). In pairwise comparisons, PB was more effective than PHT (p = 0.002), VPA was more effective than PHT (p = 0.043), and PB was more effective than LEV (p = 0.018). The most cost-effective non-BZD AED was LEV (incremental costeffectiveness ratio [ICER]: $18.55/SS), followed by VPA (ICER: $ 94.44/SS), and lastly PB (ICER: $847.22/SS). PHT and lacosamide were not cost-effective compared to the other options. Sensitivity analyses showed marked overlap in cost-effectiveness, but PHT was consistently less cost-effective than LEV, VPA, and PB. Conclusion VPA and PB were more effective than PHT for SE. There is substantial overlap in the costeffectiveness of non-BZD AEDs for SE, but available evidence does not support the preeminence of PHT, neither in terms of effectiveness nor in terms of cost-effectiveness.