LAUSR

To the Editors: We read with interest the letter from Blond et al in a recent issue of Epilepsia discussing seizure freedom with antiseizure medications (ASMs).1 The authors sought to clarify misperceptions of a 2018 article by Chen et al.2 Blond et al accurately state that a third ASM trial resulted in seizure freedom for 23.6% and that even a sixth ASM trial led to seizure freedom in 14% instead of the inaccurate assertion that individuals have only a 5% chance of seizure freedom after a second ASM.2 However, as Blond et al note in their own letter, seizure freedom is not entirely accurate, as the 2018 study definition indicated seizure control after lack of seizures for the previous 12 months or longer. The authors conclude that continued ASM trials remain of value, particularly for lessthan-ideal surgical candidates.1 Additional context helps define the challenges in suggesting additional ASM trials to drug-resistant epilepsy (DRE) patients as a meaningful path to long-term seizure freedom. When examining perhaps a natural course of DRE, Brodie et al found 16% have a “relapsing/remitting” course, a course accurately not viewed as seizure freedom.3 Callaghan et al demonstrated that remissions of at least 1 year occur in 5% of DRE patients annually, although the majority relapse.4 Furthermore, Wang et al in 2013 found that DRE patients without ASM change had a 1.66 times higher likelihood of entering remission compared to DRE patients with ASM change after covariate adjustment.5 In short, these three studies independently suggest that remissions in DRE patients occur regardless of ASM changes. In contrast, long-term epilepsy surgery outcomes prove far more robust, with 10-year seizure-free rates ranging between 33% and 47%6,7 in addition to a sharp decline in mortality risk following successful epilepsy surgery.8 When examining ASMs themselves, the Chen 2018 paper found no difference in seizure-free rates during three different time periods of the 30-year follow-up (and thus of various ASM availability), suggesting that increased ASM availability unfortunately has not resulted in greater seizure-free rates.2 Further analysis of that data found the risk of intolerable adverse events (AEs) from ASM increased with each subsequent ASM trial, particularly if an ASM had been previously changed due to an AE.9 In sum, the accurate clarification that 5% of people as a whole become seizure-free after a failed second ASM is certainly important. The misperception that an individual has a <5% seizure-free chance after that second ASM should not be perpetuated. However, using that clarification as a robust rationale for continued ASM trials is challenging when acknowledging the relapsing/remitting nature of DRE, an unchanged seizure-free rate despite increased ASM development, and the risk of new potential AEs with further ASM trials. Further ASM trials in DRE patients, although well intentioned, can likely only lead to surgical delay.10