PracticeUpdate Conference Series - ANZAN 2018

reported results for perampanel >4–8 mg and >8–12 mg daily. The most common concomitant baseline antiepileptic drugs were valproic acid (n=55), lamotrigine (n=53), levetiracetam (n=37), topiramate (n=21), and zonisamide (n=12). Patients may have received more than one of these baseline antiepileptic drugs. The most common reasons for discontin- uing were adverse events, other, and patient choice: ƒ ƒ Lamotrigine was discontinued due to patient choice by 6 of 34 patients receiving >4–8 mg daily and due to adverse events or other by 3 of 19 patients receiving >8–12 mg daily ƒ ƒ Levetiracetam was discontinued due to patient choice by 5 of 27 patients receiving >4–8 mg daily and due to adverse events by 2 of 10 patients receiving >8–12 mg daily ƒ ƒ Topiramate was discontinued due to other by 3 of 15 patients receiving >4–8 mg daily and due to adverse events or other by 1 of 6 patients who received >8–12 mg daily for both ƒ ƒ Valproic acid was discontinued due to patient choice by 6 of 38 patients receiving >4–8 mg daily and due other by 4 of 17 patients receiving >8–12 mg daily ƒ ƒ Zonisamide was discontinued due to patient choice or other by 2 of 10 patients receiving >4–8 mg daily for both. No discontinuations were recorded among patients who received >8–12 mg daily Patient-reported treatment-emergent adverse events ranged from: 88.2% (lamotrigine) to 93.3% (topiramate) for perampanel >4–8 mg daily and 70.6% (valproic acid) to 100.0% (topiramate and zonisamide) for perampanel >8–12 mg daily. The most common treatment- emergent adverse event was dizziness. Dr. O’Brien concluded that in this post hoc analysis, the primary reasons for discontinuation and the incidence of treat- ment-emergent adverse events differed between the most common baseline antiepileptic drug subgroups and the perampanel dose range, though types of treatment-emergent adverse events were similar. The data provided additional information on the safety of adjunctive perampanel in patients with idiopathic generalized epilepsy.

patients participated in the double-blind studies and 388 received perampanel for at least 1 year in the open-label extension study. In the double-blind studies, perampanel coadministered with an enzyme-inducing antiepileptic drug (carbamazepine, esli- carbazepine, oxcarbazepine, phenytoin) was associated with less efficacy than non-enzyme-inducing antiepileptic drugs due to increased clearance. This reduced efficacy was particularly evident at higher doses, though the differences were still greater than placebo in the open-label extension study. Concomitant administration of both non- enzyme-inducing antiepileptic drugs and enzyme-inducing antiepileptic drugs was associated with sustained efficacy, with slightly better efficacy during the first, second, and third years of perampanel exposure for non-enzyme-inducing antiepileptic drugs than enzyme-inducing antiepileptic drugs. Dr. Ko concluded that perampanel demon- strated good and sustained long-term efficacy against secondarily generalized seizures. Considering the recent FDA approval of perampanel as monotherapy for partial

seizures, non-enzyme-inducing antiepi- leptic drugs data may be more relevant to consider when perampanel is used as a single agent (no other enzyme-inducing antiepileptic drug) while real-world data and experience are accumulated. Terence J O'Brien, MD, MB, of Monash University in Melbourne, Victoria, and colleagues set out to assess the effect of common concomitant antiepileptic drugs during adjunctive treatment with perampanel. They performed a post hoc analysis from the open-label extension of a phase III study in patients with idiopathic generalized epilepsy. The analysis assessed the effects of the most common concomitant baseline antiepileptic drugs on discontinuation rates and treatment-emergent adverse event incidence during adjunctive treat- ment with perampanel in patients age ≥12 years with idiopathic generalized epilepsy and primary generalized tonic-clonic sei- zures in the open-label extension phase of study 332. Patients who completed the double-blind study were eligible to receive perampanel ≤12mg daily during the open-label exten- sion (6-week blinded conversion period; ≤136 weeks of maintenance). Dr. O’Brien

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ANZAN 2018 • PRACTICEUPDATE CONFERENCE SERIES 17