The Efficacy And Safety Of Brivaracetam At Different Doses For Partial-Onset Epilepsy:A Meta-Analysis Of Placebo-Controlled Studies

Objective: This meta-analysis systematically assessed the efficacy and safety of different doses of brivaracetam(BRV) compared with placebo as adjunctive therapy for adults with partial-onset epilepsy.Methods: Electronic and clinical trials databases were searched for randomized controlled trials(RCTs) of BRV published up to May 2015. We assessed the risk of bias of the included studies using the Cochrane Risk of Bias tool. The outcomes of interest included 50% responder rates, seizure freedom, the incidence of withdrawal and treatment-emergent adverse events.Results: Five trials(a total of 1,590 patients) met the inclusion criteria. Compared with placebo, 20, 50, 100 and 150 mg BRV was associated with significantly higher 50% responder rates(RR 1.63, 95% CI 1.17-2.26,P=0.004; RR 1.99, 95% CI 1.49-2.64, P<0.00001; RR 1.80, 95% CI 1.12-2.88,P=0.01; and RR 1.81, 95% CI 1.23-2.66, P=0.003; respectively). In addition, the effect of 50 mg BRV on seizure freedom was significantly different than that of placebo(RR 5.36, 95% CI 1.41-20.39, P=0.01). However, no significant differences were observed in the withdrawal rates between any dose of BRV and placebo(P>0.05). Both fatigue and nasopharyngitis were significantly associated with 20 mg BRV(RR 3.00, 95% CI 1.20-7.47; RR 5.98, 95% CI 1.36-26.34, respectively), whereas fatigue and irritability were associated with 50 mg BRV(RR 2.38, 95% CI 1.16-4.88; RR 2.95, 95%CI 1.03-8.44, respectively). Somnolence was associated with 150 mg BRV(RR 2.21, 95% CI 1.02-4.80). No significant differences among treatments were observed for the other common treatment-emergent adverse events.Conclusion: The use of BRV at doses of 20, 50,100 and 150 mg/day resulted in statistically significant reductions in seizure frequency with respect to the 50% responder rate in patients with partial-onset epilepsy. A statistically significant improvement in seizure freedom with 50 mg/day BRV was shown. BRV was reasonably tolerated by patients. These findings warrant confirmation in future studies.