Abstracts

Rationale:
In the US and Japan, perampanel is approved for POS (adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 years. Previous analyses have identified factors that may affect treatment responses, for example, high baseline seizure frequency has been associated with a poor prognosis (French JA. Epilepsy Curr 2002;2:69–71). This post hoc analysis aimed to identify potential predictive clinical factors for patients with POS achieving 26 weeks’ seizure freedom while receiving perampanel 4 mg/day in FREEDOM Study 342 (NCT03201900; Japan/South Korea).
Method:
FREEDOM was a multicenter, uncontrolled, open-label, single-arm study in untreated patients aged 12–74 years with POS, with/without secondarily generalized seizures (SGS). The 4 mg/day Treatment Phase comprised 6-week Titration and 26-week Maintenance Periods; patients experiencing seizures during Maintenance were transitioned to an 8 mg/day Treatment Phase. This analysis, based on the 4 mg/day Treatment Phase, was conducted using logistic regression to determine odds ratios (ORs) and 95% confidence intervals (CIs). Goodness of fit was measured by area under the receiver operating characteristic (ROC) curve. Baseline seizure frequency, seizure history (simple POS, complex POS, SGS), age at diagnosis, time since diagnosis, etiology (idiopathic, structural), and perampanel plasma concentration were assessed individually as continuous and/or categorical variables in univariate analyses. All variables were included in multivariate analyses with forwards, backwards, or no selection. Patients who withdrew during Titration were excluded.
Results:
Overall, 46/73 (63.0%) patients with ≥ 1 post-dose efficacy measurement remained seizure free for up to 26 weeks on perampanel 4 mg/day. In univariate analyses (Figure 1), lower baseline seizure frequency was a predictor of seizure freedom as both a continuous or categorical (≤ 2 vs >2 seizures/12 weeks) variable (P=0.0136 and P=0.0284, respectively). History of simple POS (P=0.7137), complex POS (P=0.3711), or SGS (P=0.7005), age at diagnosis (P=0.9241), time since diagnosis (P=0.1862), idiopathic (P=0.7118) or structural (P=0.9033) etiology, and perampanel plasma concentration (P=0.3940) were not predictors of seizure freedom. In multivariate analyses (no selection; baseline seizure frequency and perampanel plasma concentration as continuous variables), only lower baseline seizure frequency was a predictor of seizure freedom (OR [95% CI], 0.817 [0.696, 0.960]; P=0.0140; area under the ROC curve, 0.7483). The same model was selected using forwards or backwards selection.
Conclusion:
All models showed the best predictor for seizure freedom in Study 342 is baseline seizure frequency; the lower the baseline seizure frequency, the higher the probability of remaining seizure free. It should be noted that the small patient numbers in some groups, for example those with structural lesions (n=9), may limit interpretation for some factors.
Funding:
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Funding:
: Eisai Co., Ltd.