OBJECTIVES: To determine the efficiency, in terms of cost per number needed to treat (NNT), of third-generation antiseizure medications (ASMs) for the adjunctive treatment of focal-onset seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain.

METHODS: NNT data were calculated based on the seizure freedom endpoint (100% responder rate) obtained from pivotal clinical trials performed with cenobamate, brivaracetam, perampanel, lacosamide and eslicarbazepine acetate. The NNT was established as the inverse of the treatment responder rate minus the placebo responder rate. The cost of each ASM was calculated based on the defined daily dose (DDD) and maximum dose as indicated in their Summary of Product Characteristics. The pharmacological costs were obtained from Spanish databases (listed public prices) applying the corresponding mandatory discount. The cost per NNT for each ASM was calculated by multiplying its annual treatment cost by its NNT values.

RESULTS: The efficiency ranking, from most to least efficient, by DDD was 1) cenobamate 200mg (13.181€/NNT) > 2) brivaracetam 100mg (21.608€/NNT) > 3) eslicarbazepine acetate 800mg (47.830€/NNT) > 4) lacosamide 400mg (48.203€/NNT) > 5) perampanel 8mg (49.773€/NNT). Ranking according to maximum dose was 1) cenobamate 400mg (13.451€/NNT) > 2) eslicarbazepine acetate 1,200mg (22.719€/NNT) > 3) brivaracetam 200mg (37.814€/NNT) > 4) lacosamide 600mg (44.088,42€/NNT) > 5) perampanel 12mg (46.126€/NNT).

CONCLUSIONS: The findings show a clear link between the efficacy of third-generation ASMs available in Spain for the treatment of FOS in patients with DRE and their efficiency, facilitating determination of drug’s value contribution and decision-making in Spain. Cenobamate presents the lowest cost per NNT relative to seizure freedom, proving to be the most efficient option compared to third-generation alternatives.