Abstracts

Rationale: Lacosamide (LCM) has shown efficacy as adjunctive treatment for adults with partial-onset seizures including complex (CPS) and secondary generalized partial seizures (SGPS). The effects of LCM therapy on long-term health-related quality of life (HRQoL) and seizure severity are reported here by seizure type.Methods: Data from open-label extensions of three phase II/III trials (SP756, SP774, SP615) were pooled. All trials included the Quality of Life In Epilepsy scale (QOLIE-31), an epilepsy-specific HRQoL assessment with a 100-point range, while SP756 and SP774 also included the Seizure Severity Questionnaire (SSQ), measuring severity on a 7-point scale, as a secondary endpoint. Mean SSQ and QOLIE-31 scores were obtained at baseline of the double-blind trials and at week 48 of the open-label extensions. Mean change from baseline was calculated for patients with CPS or SGPS. Responders were defined as those patients achieving a 50% reduction in seizure frequency in the 6 months before week 48.Results: At baseline, SGPS patients (n=282) reported slightly lower QOLIE-31 scores than those with CPS (n=629). Differences were 2 3 points, with a clinically meaningful difference (based on thresholds previously defined using phase III LCM trial data) of 5.01 points for Social Functioning. SSQ scores at baseline were also slightly worse for SGPS patients (n=207) than for CPS patients (n=440), with differences of <0.4 points for most scores. At week 48, CPS responders (n=362) reported improvement for all QOLIE-31 scores, with clinically meaningful improvement in Seizure Worry (+10.81) and Social Functioning (+4.03). CPS non-responders (n=267) had substantially smaller improvement in Seizure Worry and Social Functioning, and worsening in all other scores. SGPS responders (n=183) showed clinically meaningful improvements in Seizure Worry (+13.34), Overall Quality of Life (+6.75), Social Functioning (+7.26), and the Total score (+5.36). SGPS non-responders (n=99) had meaningful improvement in Social Functioning (+4.25), but small improvements or worsening in all other scores. Differences between responders and non-responders were generally larger for SGPS patients than for CPS patients. On the SSQ, CPS responders (n=244) reported substantially improved severity scores of up to -1.16 on the overall score, whereas non-responders (n=196) reported changes of up to -0.54. SGPS responders (n=132) reported improvements of up to -1.24 for the overall score compared with smaller improvements of up to -0.63 for non-responders (n=75). Differences between seizure types were negligible.Conclusions: Long-term LCM therapy was associated with clinically meaningful improvements in HRQoL and substantial reductions in seizure severity that were greater for those patients who had achieved a 50% reduction in seizure frequency compared with non-responders. SGPS responders reported greater improvements on the QOLIE-31 than CPS responders, leading to similar HRQoL scores at 1 year between seizure groups despite worse baseline scores in SGPS patients. Study funded by UCB