Abstracts

Rationale: A MCID is defined as a Hr-QoL score change that represents a clinically meaningful improvement or worsening in a patient s health status as a result of a treatment change compared to other treatment options. We evaluated the relationship between Hr-QoL and the proportions of PER responders who achieved a MCID in refractory POS treatment. Methods: The quality of life in epilepsy (QOLIE)-31 questionnaire was administered to patients with treatment refractory POS pooled from three phase III randomized, placebo-controlled trials (304, 305 and 306) of once-daily adjunctive PER 4-12 mg. PER 2 mg was not included because it was not efficacious. The relationship between Hr-QoL and responders who achieved a MCID was calculated by multiplying the 50% and 75% responder rates (defined as patients with a 50% or 75% seizure reduction) by the proportions of patients who achieved the MCID threshold for each QOLIE-31 subscale: seizure-worry (7.42), cognitive functioning (5.34), emotional well-being (4.76), social functioning (3.95), energy/fatigue (5.25), medication effects (5.00), and overall quality of life (6.42). The MCID thresholds used in this analysis were derived from a similarly severe, refractory POS population by Borghs, et al. A Chi-Square Cochrane-Mantel-Haenszel statistical test was applied to test for significant differences between proportions. Results: Eight hundred thirty-two evaluable patients completed the QOLIE-31 questionnaire. In 50% responders, the subscales associated with the smallest and largest proportions of patients who achieved a MCID were emotional well-being (36.5%) and seizure-worry (52.4%). Among 50% responders, the seizure-worry (52.4%), medication effects (50.4%) and social functioning (49.6%) subscales most commonly were associated with a MCID in all PER treatment groups (4mg, 8mg, and 12mg). The PER 8mg group (N=431) had the largest proportions of patients who achieved a MCID for the same subscales at 18.5%, 17.8%, and 17.5%, respectively, vs. placebo at 10.1%, 9.7%, and 9.6%, respectively, (p<0.0001). In 75% responders, the subscales associated with the smallest and largest proportions of patients who achieved a MCID were energy/fatigue (42.6%) and medication effects (55.0%). Among 75% responders, relatively smaller proportions of patients achieved a MCID in all PER treatment groups with the 8mg group having the largest relative proportion at 17.4% vs. placebo at 6.1% (p<0.0001). Conclusions: In 50% and 75% PER responders, a MCID was most commonly achieved in the seizure-worry, medication effects, and social functioning subscales of the QOLIE-31 questionnaire. Overall, the three QOLIE-31 questionnaire subscales of seizure-worry, medication effects, and social functioning were associated with the largest proportions of PER responders who achieved a MCID.