RELATIVE EFFICACY AND TOLERABILITY OF LACOSAMIDE VERSUS LEVETIRACETAM AS MONOTHERAPY FOR ADULTS WITH NEWLY DIAGNOSED FOCAL SEIZURES- A POST-HOC ANALYSIS OF RANDOMIZED CLINICAL TRIALS
Author(s)
Kroep S1, Bouwmeester W1, Zhang Y2, Dimova S3, Noack-Rink M4, Borghs S5, Charokopou M3
1Pharmerit International, Rotterdam, The Netherlands, 2UCB Pharma, Raleigh, NC, USA, 3UCB Pharma, Brussels, Belgium, 4UCB Pharma, Monheim am Rhein, Germany, 5UCB Pharma, Slough, UK
OBJECTIVES: Lacosamide was previously compared to other anti-epileptic monotherapies in adults with focal seizures in a network meta-analysis (NMA). The number of clinical trials in this NMA was too limited to assess the impact of heterogeneity on outcomes. To overcome the similarity assumption of the NMA, we performed a patient level data analysis of lacosamide and levetiracetam in newly-diagnosed adult epilepsy patients. METHODS: Pooled patient-level data from two clinical trials –evaluating lacosamide and levetiracetam monotherapy versus controlled-release carbamazepine (carbamazepine-CR)– were analyzed to assess efficacy (6 and 12-month seizure-freedom) and tolerability (discontinuations due to adverse events [AEs]) outcomes. A propensity score was calculated to adjust for confounding factors. Carbamazepine-CR arm outcomes were compared to assess residual confounding in the lacosamide-levetiracetam comparison. RESULTS: In total, 444 and 285 patients were treated with lacosamide and levetiracetam. Lacosamide treatment resulted in a higher probability of being seizure free for 6-months (OR 0.69; 95%CI 0.44-1.08 for not being seizure free) and a lower risk of discontinuations due to AEs (OR 0.59; 95%CI 0.31-1.11) compared to levetiracetam. After adjusting for confounding factors, patients treated with carbamazepine-CR in the lacosamide trial had a higher probability of being seizure free for 6-months (OR 0.81; 95%CI 0.50-1.32) and lower risk of discontinuations due to AEs (OR 0.55; 95%CI 0.32-0.95) compared to patients treated with carbamazepine-CR in the levetiracetam trial. These results were consistent in various propensity score models, subgroup analyses and 12-months seizure freedom outcomes. CONCLUSIONS: Carbamazepine-CR outcomes differed between the trials after propensity score adjustment, indicating residual confounding that prevents a meaningful lacosamide-levetiracetam comparison. Comparative assessments derived from NMAs are not biased by such confounding (randomization holds); however, they describe the average treatment effect in a population without reflecting on differences in treatment response between individuals and subgroups of patients with distinct epilepsy characteristics.
Conference/Value in Health Info
2017-11, ISPOR Europe 2017, Glasgow, Scotland
Value in Health, Vol. 20, No. 9 (October 2017)
Code
PND4
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Neurological Disorders