Effectiveness of Antiseizure Medication Triple Therapy in Patients with Glioma with Refractory Epilepsy

Background: About 10% of glioma patients with epilepsy need antiseizure medication (ASM) triple-therapy due to refractory epilepsy. Aim of this study was to evaluate whether levetiracetam combined with valproic acid and clobazam (LEV+VPA+CLB), a frequently prescribed triple-therapy, has favorable effectiveness compared to other triple-therapy combinations in glioma patients. Methods: This was a multicenter retrospective observational cohort study, with as primary outcome the cumulative incidence of time to treatment failure for any reason, from start of ASM triple-therapy treatment. Secondary outcomes included cumulative incidences of: 1) time to treatment failure due to uncontrolled seizures; 2) time to treatment failure due to adverse effects; and 3) time to recurrent seizure. Patients were followed for a max. duration of 36 months. Results: Out of n=1435 patients in the original cohort, n=90 patients received ASM triple-therapy after second-line ASM treatment failure due to uncontrolled seizures. LEV+VPA+CLB was prescribed to 48% (43/90) and other ASM triple-therapy to 52% (47/90) patients. The cumulative incidence of treatment failure for any reason of LEV+VPA+CLB did not significantly differ from other ASM triple-therapy combinations (12 months: 47% [95%CI, 31-62%] versus 42% [95%CI, 27-56%], p=0.892). No statistical significant differences for treatment failure due to uncontrolled seizures (12 months: 12% [95%CI, 4-25%] versus 18% [95%CI, 8-30%], p=0.445), due to adverse effects (12 months: 22% [95%CI, 11-36%] versus 15% [95%CI, 7-27%], p=0.446), or recurrent seizure (1 month: 65% [95%CI, 48-78%] versus 63% [95%CI, 47-75%], p=0.911) were found. Conclusions: LEV+VPA+CLB might show equivalent effectiveness compared to other ASM triple-therapy combinations in glioma patients. Classification of evidence: This study provides Class III evidence that for glioma patients with refractory epilepsy on triple-therapy ASMs, LEV+VPA+CLB demonstrated similar effectiveness and tolerability compared to other ASM triple-therapy combinations.