Abstracts

Rationale: Lacosamide (LCM) is an antiepileptic drug (AED) approved for the adjunctive treatment of adults with partial-onset seizures. Previous exploratory analyses of pooled data from three Phase II/III trials (SP667, SP754, SP755) evaluated efficacy and safety of LCM in patients grouped by the sodium channel-blocking (SCB) properties of their concomitant AEDs. The present analysis evaluates a health-related quality of life (HRQoL) measure in these same SCB subgroups.Methods: In all three trials, the Quality of Life In Epilepsy scale (QOLIE-31), an epilepsy-specific HRQoL assessment with a 100-point range, was included as a secondary endpoint. Mean QOLIE-31 score changes from baseline to end of maintenance, carrying the last observation forward for patients who left the trials, were evaluated. Patients were assigned to one of two groups: SCB+ (those with at least one traditional SCB concomitant AED at baseline [carbamazepine, lamotrigine, oxcarbazepine and/or phenytoin derivatives]) or SCB-. Clinically meaningful change was defined using previously estimated QOLIE-31 cutoff scores.Results: Of 1046 patients with QOLIE-31 data, 868 (83%) met SCB+ criteria. In this SCB+ group, LCM 200 or 400mg/d (n=174, n=317) groups showed largest improvements on Seizure Worry (+6.42, +6.31), but worsening on Medication Effects (400mg/d; -4.26). On other subscales slight improvements were seen. Patients randomized to LCM 600mg/d (n=121) showed worsening (-1 to -3.57) on all subscales except Seizure Worry (+4.72); worsening on Energy/Fatigue (-5.7) could be deemed clinically meaningful. Patients randomized to PBO (n=256) showed non-clinically meaningful improvements (up to +3.26). In the SCB- group, LCM 200mg/d (n=40) was associated with clinically meaningful improvement on Social Functioning (+4.17), improvement on Seizure worry (+5.37) and worsening on Energy/Fatigue, Medication Effects and Emotional Well-being, none of which were clinically meaningful. Improvements on all subscales except Medication Effects (-4.21) were observed among patients taking LCM 400mg/d (n=67). LCM 600mg/d (n=19) showed marked clinically meaningful improvements on Seizure worry (+25.04) and Social Functioning (+9.78), improvements on Medication Effects (+4.39), the Total score (+3.97) and Energy/Fatigue (+3.68) and no improvement on other subscales. PBO patients showed improvements on all subscales of up to +4.25. Conclusions: In this post hoc exploratory analysis, the impact of LCM on QOLIE-31 subscales was dependent upon dose and the sodium channel properties of the concomitant AED regimen. Adding LCM up to 400mg/d to the treatment of patients with any combination of AED led to generally stable HRQoL. Largest differences between subgroups were noted among patients treated with LCM 600mg/d, with marked clinically meaningful improvements on Seizure Worry and Social Functioning subscales in SCB- patients receiving LCM 600mg/d and clinically meaningful worsening on the Energy/Fatigue subscale in SCB+ patients receiving LCM 600mg/d. Study funded by UCB