Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug‐resistant focal epilepsy

Abstract

Summary Objective Although many studies have attempted to describe treatment outcomes in patients with drug‐resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug‐resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. Methods This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug‐resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). Results A seizure‐free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a “treatment failure” as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as “undetermined outcome” (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug‐resistant by the EP. Significance This study validates the use of ILAE treatment outcome criteria in a real‐life setting, providing validated estimates of seizure freedom in patients with drug‐resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases.

Starting a new anti‐seizure medication in drug‐resistant epilepsy: Add‐on or substitute?

“…In our study, new ASMs were introduced by substitution and addition equally. Comparison of the two strategies showed no difference for efficacy outcomes, with a quarter achieving at least a 12‐month period of 50% or greater seizure reduction in both groups, and with 6% achieving seizure freedom for at least 12 months, seizure outcomes that were comparable to those seen in randomized and observational studies 2‐4,8,11 . Although physician differences in using one strategy over another were present, these were not associated with any difference in seizure outcomes, providing reassurance that individual preference of ASM and method of introduction may be less important than previously thought 5‐7 .…”

Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

“…In due course, we may come to discover that there are many mechanisms or contributors to drug resistance. For now, it is reassuring that categorization according to the definition has proven to be dependable in practice (Mula et al, 2019;Zaccara et al, 2019).…”

Critical Appraisal of Cenobamate as Adjunctive Treatment of Focal Seizures in Adults

“…Data from Vernillett et al, 15 Roberti et al 7 to respond to the first ASM exponentially decays with the number of drug trials. 3,23 For example, the percentage of seizure free patients is about 4.4% after the third ASM regimen. 24 Since the time elapsed from diagnosis to randomization in patients recruited in the CNB clinical studies was around 20 years, 18,19 it can be hypothesized that a great number of patients had several unsuccessful drug trials before entering the trials and this enhances further the good efficacy profile of CNB.…”