The effectiveness of antiepileptic drug tripletherapy in refractory epileptic glioma patients: a multicenter observational cohort study

Abstract Background About 10% of the glioma patients need antiepileptic drug (AED) tripletherapy due to refractory epilepsy. This study aimed to determine whether levetiracetam combined with valproic acid and clobazam (LEV+VPA+CLB), a commonly prescribed tripletherapy, has favourable effectiveness compared to other tripletherapy combinations in glioma patients. Material and Methods In this multicenter retrospective observational cohort study, the primary outcome was the cumulative incidence of treatment failure for any reason, from initiation of AED tripletherapy. Secondary outcomes included cumulative incidences of: 1) treatment failure due to uncontrolled seizures; 2) treatment failure due to adverse effects; and 3) recurrent seizure. Maximum duration of follow-up was 36 months. Results Ninety patients, from an initial cohort of n=1435 patients, received AED tripletherapy after second-line AED duotherapy treatment failure due to uncontrolled seizures. LEV+VPA+CLB was prescribed to 43 (48%) and other AED tripletherapy to 47 (52%) patients. The cumulative incidence of treatment failure for any reason of LEV+VPA+CLB did not significantly differ from other tripletherapy 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. Conclusion LEV+VPA+CLB has not shown favourable efficacy or tolerability compared to other AED tripletherapy combinations in glioma patients. Therefore, we cannot specifically recommend CLB as tripletherapy add-on AED to LEV+VPA.