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Abstract
Objective
To evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.
Materials and methods
PubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence.
Results
A total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50–1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79–1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34–5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51–2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90–1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41–0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea.
Conclusion
LEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness.
Registered number
PROSPERO (No CRD 42017069367).
Acknowledgments
We extend special thanks to Wei Huang from Zhejiang Province Chinese Medical Hospital, Le Gao, Ji-Chun Yang and Yang Xu from Peking University Health Science Center as well as Jun-Wen Zhou from the Public Health Department, and Aix-Marseille University for their contribution in conducting the literature review and drafting figures for this manuscript. We would like to thank Li Wang from Peking University First Hospital and Yuan Zhang from McMaster University for expert consultation. This study was funded by UCB China Inc. At no point did UCB China Inc. attempt to influence the manuscript. The abstract of this paper was presented as a poster in the ISPE’s 11th Asian Conference on Pharmacoepidemiology with interim findings.
Disclosure
The authors report no conflicts of interest in this work.