Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug (ASD) for partial-onset seizures (POS) and primary generalized tonic-clonic (PGTC) 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, the Carle Foundation Hospital in Urbana, Illinois, US (known as Site #1001), 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 73 pts at Site #1001 (mean [standard deviation (SD)] age, 30.8 [12.5] years; 50.7% female) and 1620 at all other sites (mean [SD] age, 28.4 [16.7] years; 52.8% female). Most common seizure types were complex POS (Site #1001, n=46 [63.9%]; other sites, n=952 [58.8%]) and PGTC (n=48 [66.7%] and n=810 [50.1%], respectively). Most pts received 1-3 Baseline ASDs (Site #1001, 86.3%; other sites, 73.9%); 34.2% and 19.4% were on enzyme-inducing ASDs, respectively. At completion, 64.4% (n=47; Site #1001) and 50.1% (n=812, other sites) of pts remained on perampanel.Perampanel was uptitrated weekly (1.4% [Site #1001]; 19.4% [other sites]), biweekly (43.8%; 17.6%), every 3 weeks (0%; 1.7%), other (49.3%; 52.2%), and unknown (5.5%; 9.1%). Mean (SD, range) maximum daily perampanel doses were 9.3 (4.5, 2-22; Site #1001) and 6.5 (3.3, 0-52; other sites) mg; mean (SD, range) daily doses were 7.9 (3.9, 2.0-14.1) and 5.5 (2.9, 0.1-52.0) mg, respectively; mean (SD, range) cumulative duration of perampanel exposure was 22.2 (16.5, 0-54.6) and 16.9 (15.5, 0-77.1) months, respectively.Retention and 50% responder rates were generally higher at Site #1001 vs other sites (Figure 1). At Months 22-24, median reductions in seizure frequency/28 days were 100% (Site #1001; n=6) and 86.7% (other sites; n=45).TEAEs occurred in 50 (68.5%) pts at Site #1001 and 621 (38.3%) at other sites (Table 1). Conclusions: There was moderate variability in retention rate and dosing experience for perampanel use between Site #1001 and all other study sites; greater variability was observed in efficacy and safety. 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.