Pregabalin or placebo used adjunctively with levetiracetam in refractory partial-onset epilepsy: a post hoc efficacy and safety analysis in combined clinical trials

Abstract

Objective:

Some patients with epilepsy require treatment with >1 adjunctive antiepileptic drug (AED) to achieve adequate seizure remission. The purpose of this analysis was to evaluate the efficacy and safety of adding adjunctive pregabalin to an AED regimen that included levetiracetam in patients with refractory partial-onset epilepsy.

Research design and methods:

Data from the pregabalin and placebo arms of two placebo-controlled, double-blind, randomized studies of pregabalin in patients who received adjunctive treatment with levetiracetam in addition to ≥1 other AEDs were pooled for this post hoc analysis. Patients (aged ≥18 years) had ≥4 partial-onset seizures and no 28-day period free of seizures during baseline. Efficacy outcomes included Response Ratio (RRatio), change from baseline in seizure frequency, proportion of patients with ≥50% reduction in seizure frequency, and 28-day seizure-freedom rate. Safety was evaluated using adverse events (AEs).

Results:

In total, 138 patients were included in the analysis (placebo, n = 47; pregabalin, n = 91). Pregabalin was significantly better than placebo for difference in least squares mean of the RRatio (−16.4; 95% confidence interval [CI]: −28.5, −4.5; p = 0.0085), median of the difference in percentage change from baseline in seizure frequency (−22.3; 95% CI: −40.1, −7.2; p = 0.0095), and proportion of 50% responders (36.3 vs. 17.0; odds ratio, 3.2; 95% CI: 1.3, 8.3; p = 0.018), but not 28-day seizure-freedom rate (7 [7.7%] vs. 2 [4.3%]; p = 0.353). The most common AEs when adding pregabalin were dizziness/vertigo, fatigue, somnolence, blurred vision, and increased weight that were not proportional to the number of concomitant AEDs.

Conclusions:

In this population of patients with refractory partial-onset seizures, adding pregabalin to an AED regimen with levetiracetam produced further seizure reductions. The safety profile of pregabalin in patients receiving levetiracetam and ≥1 other AEDs did not appear to be compromised by the number of concomitant AEDs.

Key words::

• Antiepileptic drugs
• Combination therapy
• Epilepsy
• Levetiracetam
• Pregabalin
• Seizure

Transparency

Declaration of funding

This post hoc analysis and all of the original studies were funded by Pfizer Inc. Editorial support for development of this manuscript was funded by Pfizer Inc.

Declaration of financial/other interests

In the last 2 years, B.U. has no financial conflict of interest to declare in relation to the current study drug or its manufacturer, Pfizer Inc or other manufacturers of therapeutics. M.A., B.E., S.G., and T.L. were full-time employees of Pfizer Inc at the time this analysis was conducted. CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

Editorial support was provided by Thomas Hedberg and Alison Gagnon of UBC Scientific Solutions and funded by Pfizer Inc.

Some of the results of this analysis were presented at: the American Epilepsy Society 62nd Annual Meeting, December 3–5, 2008, Seattle, WA, USA; the International Epilepsy Congress 28th Biennial Congress, June 28–July 2, 2009, Budapest, Hungary; and the American Epilepsy Society 63rd Annual Meeting, December 4–8, 2009, Boston, MA, USA.