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, Duke University Medical Center in Durham, North Carolina, US (known as Site #1023), 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 178 pts at Site #1023 (mean [standard deviation (SD)] age, 28.4 [16.9] years; 52.2% female) and 1515 at all other sites (mean [SD] age, 28.6 [16.5] years; 52.7% female). The most common seizure type was complex POS (Site #1023, n=129 [72.5%]; other sites, n=869 [57.5%]). Most pts received 1-3 Baseline ASDs (Site #1023, 44.4%; other sites, 78.0%); 7.9% and 21.5% were on enzyme-inducing ASDs, respectively. At completion (March 15, 2019), 50.6% (n=90; Site #1023) and 50.8% (n=769; other sites) of pts remained on perampanel.Perampanel was uptitrated weekly (0.6% [Site #1023] vs 20.8% [other sites]), biweekly (2.2% vs 20.7%), every 3 weeks (0.0% vs 1.8%), 'other' (97.2% vs 46.7%), and 'unknown' (0.0% vs 10.0%). Mean (SD, range) maximum daily perampanel doses were 6.3 (2.7, 0-14; Site #1023) and 6.7 (3.4, 0-52; other sites) mg; mean (SD, range) daily doses were 6.3 (2.7, 0.1-14.0) and 5.5 (3.0, 0.3-52.0) mg, respectively; mean (SD, range) cumulative duration of exposure was 17.3 (16.0, 0.0-62.7) and 17.1 (15.5, 0.0-77.1) months, respectively.Retention rates over 24 months were similar; 32.5% (Site #1023) and 53.4% (other sites) of pts improved on perampanel based on investigator impression of seizure effect (Figure 1). No seizure frequency data were recorded at Site #1023.TEAEs occurred in 38 (21.3%) pts at Site #1023 and 633 (41.8%) at other sites (Table 1). Conclusions: There was little variability in retention and drug exposure for perampanel use between Site #1023 and all other study sites; however, variations in titration, efficacy, and TEAEs were reported. 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.