PracticeUpdate Neurology June 2019

EDITOR’S PICKS 9

Validated Outcome of Treatment Changes According to International League Against Epilepsy Criteria in Adults With Drug-Resistant Focal Epilepsy Epilepsia Take-home message • After a 2010 ad hoc task force report of the International League Against Epilepsy (ILAE) proposed a new definition of drug- resistant epilepsy, treatment providers have employed new working concepts in caring for patients with epilepsy. The definitions provided included two hierarchical levels of anti-epileptic drug response as well as the term “pseudo-drug resistance,” as well as a formal definition of seizure freedom. Extending this previous report, the authors present a multicenter study of 1052 patients with presumed drug-resistant focal epilepsy with the aim of investigating the validity of these definitions in clinical practice. Assessing the patients at multiple 6-month intervals for up to 34 months, investigators rated drug resistance status and treatment outcomes according to the ILAE criteria; at least 2 independent members of an external expert panel provided review. While the results supported the validity of the outcome criteria, the authors also made note of some interesting findings. Seizure freedom after two failed drugs was 11.8%, and this fell to 2.6% after six failures. In addition, almost 20% of patients were deemed pseudo-drug resistant. • This is an interesting study. It validates the 2010 ILAE criteria of drug-resistant epilepsy as well as terms used for seizure freedom. In addition, it identifies less chance of success with more drug trials. Interestingly, there is a significant contrast in the perception of seizure freedom among practitioners. Omar Iqbal Khan MD

Abstract 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 investi- gators. 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 hav- ing 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 crite- ria 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. Validated Outcome of Treatment Changes According to International League Against Epilepsy Criteria in Adults With Drug-Resistant Focal Epilepsy. Epilepsia 2019 Mar 13;[EPub Ahead of Print], M Mula, G Zaccara, CA Galimberti, et al. www.practiceupdate.com/c/81307

COMMENT By Sara Inati MD T his prospective, multicenter study provides validated estimates of seizure outcomes in 1053 adults with drug- resistant focal epilepsy (DRE), followed for up to 34 months after the introduction of an additional antiepileptic drug (AED) into their treatment regimen. Utilizing the International League Against Epilepsy (ILAE) 2010 criteria for drug resistance and treatment outcomes, the researchers found that, overall, fewer than 10% of patients achieved seizure freedom (from 11.8% after two failed AEDs to 2.6% with more than six failed AEDs). These outcome data will be valuable when counseling patients about the risks and benefits of additional trials of AEDs in comparison with invasive procedures, such as surgery. This study additionally highlights the ongoing difficulty in identifying which patients have DRE, a distinction with important clinical implications such as consideration of referral to an epilepsy center. In this study, outcomes were assessed independently by study investigators and an expert panel. Overall agreement was 70.4%, with the panel labeling significantly fewer patients as treatment failures and more as having “undetermined outcomes.” These patients with “pseudo drug resistance” may respond differently to new treatment interventions, and this designation may also explain some of the variability in responses to interventions seen during clinical trials in epilepsy. Dr. Inati is Chief of the EEG Section and Director of the Epilepsy Service of the Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.

VOL. 4 • NO. 2 • 2019