PROVE: Retrospective, non‐interventional, Phase IV study of perampanel in real‐world clinical care of patients with epilepsy

Abstract

Objective To assess retention, dosing, efficacy, and safety of perampanel in a large cohort of patients with epilepsy during routine clinical care. Methods PROVE was a retrospective, non‐interventional Phase IV study (NCT03208660). Data were obtained retrospectively from the medical records of patients in the United States initiating perampanel after January 1, 2014, according to treating clinicians' recommendation. Retention rate was the primary efficacy endpoint. Secondary efficacy endpoints included median percent changes in seizure frequency per 28 days from baseline, seizure‐freedom rate, and overall investigator impression of seizure effect. Safety endpoints included incidence of treatment‐emergent adverse events (TEAEs). Efficacy and safety were also assessed according to baseline use of enzyme‐inducing antiseizure medications (EIASMs). Results Overall, 1703 patients were enrolled and included in the Safety Analysis Set (SAS; ≥1 baseline EIASMs, n = 358 [21.0%]; no baseline EIASMs, n = 1345 [79.0%]). Mean (standard deviation [SD]) cumulative duration of exposure to perampanel was 17.4 (15.7) months; mean (SD) daily perampanel dose was 5.6 (2.7) mg. The most frequent perampanel titration intervals were weekly (23.4%) and every 2 weeks (24.7%). Across the SAS, 24‐month retention rate was 48.1% (n = 501/1042). Based on overall investigator impression at the end of treatment, 51.9%, 35.8%, and 12.3% of patients in the SAS experienced improvement, no change, or worsening of seizures, respectively. TEAEs occurred in 704 (41.3%) patients; 79 (4.6%) had serious TEAEs. The most common TEAE was dizziness (7.3%). There was some variation in efficacy according to EIASM use, while retention rates and safety were generally consistent. Significance In this final analysis of >1700 patients with epilepsy receiving perampanel in routine clinical care, favorable retention and sustained efficacy were demonstrated for ≥12 months.

PROVE—Phase IV Study of Perampanel in Real-World Clinical Care of Patients with Epilepsy: Interim Analysis in Pediatric Patients

“…In addition, these data suggest that daily oral doses of perampanel are generally well tolerated in preadolescent and adolescent patients, and TEAEs reported in these populations were generally consistent with the known safety profile of perampanel, 1,2,10 as well as those reported in the overall PROVE Study population, 16,17 and resolved after treatment discontinuation. TEAEs related to hostility and/or aggression have been previously reported in patients treated with perampanel.…”

“…However, the most common modal daily doses were similar across analyses. 16,17 It should be noted that doses used in this analysis are lower than the maximum approved dose (12 mg/d), suggesting that some preadolescent and adolescent patients benefit from treatment with the lower perampanel doses without the need for further titration up to the maximum allowed perampanel doses. In this real-world population, the most common titration schedules listed for both preadolescent and adolescent patients were 'other' (i.e., not weekly/biweekly/ every 3 weeks), followed by biweekly, and then weekly.…”

Long-term treatment with Perampanel of Chinese patients with focal-onset seizures, especially in sleep-related epilepsy: a prospective real-world observational study

“…Our results support the findings of previous studies ( 25 , 26 ), indicating that the efficacy and safety of PER remain consistent, regardless of the baseline use of EIASMs. However, patients who are prescribed EIASMs usually need a higher dose of PER than those who are not prescribed EIASMs, to achieve an effective treatment outcome.…”

Comparison of the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children and adolescents with newly diagnosed focal epilepsy

“…Additionally, a real-life experience demonstrated that PER monotherapy seems effective and well tolerated in 20 patients, aged between 8 and 10, with childhood absence seizures ( Operto et al, 2020b ; Operto et al, 2022 ). Furthermore, clinical experience with PER monotherapy has mainly been addressed in adult patients ( Yamamoto et al, 2020 ; Chinvarun, 2022 ; Wechsler et al, 2022 ). Efficacy in adults can be extrapolated to children aged 4 years and older.…”