1. Long term effectiveness of perampanel: the Leeds experience Jo Geldard, Melissa Maguire, Elizabeth Wright, Peter Goulding Leeds General Infirmary, Leeds
Introduction
Perampanel (PRM) is a unique adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients with epilepsy aged 12 years and older. The drug was approved in the EU in March 2011.
Clinicians in the UK have been prescribing PRM since 2013 and therefore it seemed timely to assess the long term effectiveness and tolerability of perampanel in Leeds.
This is a prospective evaluation of the long term use of perampanel in adult patients in Leeds.
Data was collected from patients attending the epilepsy clinic. Patients had taken perampanel for a period of 12 months.
These are preliminary data of a subset of 41 patients taking perampanel for 12 months on whom we have complete data.
Method
Results
We collected data on 41 patients. The median age was 46 years (range 16 to 75 years). There were 22 males (54%) and 19 females (46%). Patients were diagnosed with focal seizures (FS) and / or tonic-clonic (TC) seizures.
The median daily dose of PRM was 8mgs (range 4-12mgs). The median number of other AEDs patients were taking on starting PRM was 2 (range1 to 4). Mean number of AEDs previously used was 9 (range 2-12).
An ≥ 50% reduction in seizure frequency from baseline was achieved in 46% of patients with TC seizures, 50% with focal seizures after 12 months of treatment with PRM. Overall 53% had a ≥ 50% reduction in seizure frequency.
Seizure freedom from TC seizures was achieved in 2 patients (18%) after 12 months of treatment with
The most common adverse events (AEs) were sedation (34%), dizziness (31%) and ataxia (24%).
No serious adverse were identified.19% of patients reported however this was not severe enough to warrant discontinuation of PRM.
73 % of the ≥ 50% responders were noted to be taking concomitant carbamazepine (CBZ).
Results
Figure 1: Percentage of patients with ≥50% reduction in seizures and seizure freedom after twelve months of treatment with PRM
Table 2: Comparison of findings from Clinical Trials and this Service Evaluation (pooled across doses and seizure types)
Clinical Trials [1-3] (pooled mean across doses)
Service Evaluation
After 12 months of treatment with PRM
Patients with ≥50% reduction in seizure frequency (%) 30 53
Patients achieving seizure freedom (%) 4 5
Table 1: Seizure frequency at baseline, at 3 months and after 12 months with treatment of PRM
Seizure frequency
Baseline
(3 months prior to commencing drug)
at 3 months treatment
After 12 months treatment
Seizure type
Median (range) TC
5 (1-72)
0 (0-28)
0 (0-72)
Focal
36 (1-1800)
22 (1-355)
21 (1-540)
Discussion
Discussion
The median number of antiepileptic drugs taken when PRM was commenced was 2 and the median number previously tried was 9. Therefore, this was a generally difficult to treat sample of epilepsy patients with refractory epilepsy.
The percentage of patients with ≥50% responder rate was similar to open label studies. A similar percentage of patients achieved seizure freedom compared with open label studies.
The most common AEs were sedation, dizziness and ataxia .
In conclusion there is evidence that PRM is a useful add-on drug for patients with refractory partial onset epilepsy. Though not statistically significant (p-value 0.08) there was a trend towards a synergistic effect between CBZ and PRM which requires further investigation.
References:
French JA, Krauss GL, Biton V et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase 111 study 304. Neurology 2012; 79:
French J, Krauss GL,Steinoff BJ et al. Evaluation of adjuvant perampanel in patients with refractory partial-onset seizures: results of randomised global phase 111 study 305. Epilepsia 2013;
Krauss GL, Serratosa JM, Villanueva V et al. Randomised phase 111 study 306; adjunctive perampanel for partial-onset seizures. Neurology 2012: 78: 14
Steinhoff BJ et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures ; a pooled analysis of three Phase III studies. Epilepsia 2013: 54(8) :1481-9
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