Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug (ASD) for partial-onset seizures (POS) and primary generalized tonic-clonic seizures. There are limited data on real-world use of perampanel as an ASD in the US. PROVE (Study 506; NCT03208660) is a retrospective, multicenter, non-interventional Phase IV study of perampanel administered to patients (pts) with epilepsy during routine clinical care. Here, we report a post hoc analysis of the data from PROVE to assess whether regional differences existed in retention rate, safety, efficacy, and dosing experience between pts treated with perampanel at a single study site, Le Bonheur Children's Hospital in Memphis, Tennessee, US (known as Site #1007), and pts treated with perampanel across all other study sites. Methods: Data were obtained from medical records of pts who initiated perampanel treatment after January 1, 2014. Follow-up was completed on March 15, 2019. Based on the Safety Analysis Set (SAS), the primary endpoint was retention rate (proportion of pts remaining on perampanel at 3, 6, 12, 18, and 24 months following treatment initiation). Dosing experience, efficacy, and safety (including monitoring of treatment-emergent adverse events [TEAEs]) were secondary objectives. Results: SAS included 125 pts at Site #1007 (mean [standard deviation (SD)] age, 12.0 [7.4] years; 44.8% female) and 1568 at all other sites (mean [SD] age, 29.9 [16.4] years; 53.3% female). Most common seizure types were complex POS (Site #1007, n=53 [42.4%]; other sites, n=945 [60.4%]) and PGTC (n=50 [40.0%] and n=808 [51.6%], respectively). Most pts received 1-3 Baseline ASDs (Site #1007, 83.2%; all other sites, 73.7%); 12.0% and 20.7% received enzyme-inducing ASDs, respectively. At completion, 55.2% (n=69; Site #1007) and 50.4% (n=790; other sites) of pts remained on perampanel.Perampanel was uptitrated weekly (12.8% [Site #1007]; 19.1% [other sites]), biweekly (39.2%; 17.1%), every 3 weeks (4.0%; 1.5%), 'other' (4.8%; 55.8%), and 'unknown' (39.2%; 6.5%). Mean (SD, range) maximum daily perampanel doses were 6.7 (3.6, 1-20; Site #1007) and 6.6 (3.4, 0-52; other sites) mg; mean (SD, range) daily doses were 5.2 (2.9, 0.7-13.8) and 5.6 (3.0, 0.1-52.0) mg, respectively; mean (SD, range) cumulative duration of exposure was 17.5 (15.2, 0.4-75.5) and 17.1 (15.6, 0.0-77.1) months, respectively.Retention and 50% responder rates were similar for Site #1007 and other sites (Figure 1). At Months 22-24, median reductions in seizure frequency/28 days were 93.5% (Site #1007; n=6) and 86.9% (other sites; n=45).TEAEs occurred in 56 (44.8%) pts at Site #1007 and 615 (39.2%) at other sites (Table 1). Conclusions: There was little variability in retention rate, dosing experience, efficacy, and safety profile for perampanel use between a study site in Tennessee (Site #1007) and all other study sites. The recent approval of perampanel monotherapy for POS and potential for earlier perampanel use may affect regional variability. Additional analyses are planned to further investigate outcomes of perampanel use between specific PROVE study sites to establish whether regional differences do indeed exist.  Funding: Eisai Inc.