Francesco Brigo1, Nicola Luigi Bragazzi2, Raffaele Nardone3, Eugen Trinka4. 1. Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Italy; Division of Neurology, Franz Tappeiner Hospital, Merano, Italy. Electronic address: dr.francescobrigo@gmail.com. 2. School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy. 3. Division of Neurology, Franz Tappeiner Hospital, Merano, Italy; Department of Neurology, Christian Doppler Medical Centre, Paracelsus Medical University, Salzburg, Austria. 4. Department of Neurology, Christian Doppler Medical Centre, Paracelsus Medical University, Salzburg, Austria; Center for Cognitive Neuroscience, Salzburg, Austria; University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria.
Abstract
BACKGROUND: Brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) have been recently marketed as adjunctive treatments for focal onset seizures. To date, no randomized controlled trial (RCT) has directly compared BRV with ESL, LCM, or PER. PURPOSE: To compare BRV with the other add-on AEDs in patients with uncontrolled focal epilepsy, estimating their efficacy and tolerability through an adjusted, common-reference based indirect comparison meta-analysis. METHODS: We systematically searched RCTs in which add-on treatment with ESL or LCM in patients with focal onset seizures have been compared with placebo. Efficacy and tolerability outcomes were considered. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy of BRV, LCM, ESL, or PER versus placebo. Adjusted indirect comparisons were then made between BRV and the other three AEDs using the obtained results, comparing the minimum and the highest effective recommended daily dose of each drug. RESULTS: Seventeen RCTs, with a total of 4971 patients were included. After adjusting for dose-effects, indirect comparisons showed no difference between BRV and LCM, ESL, or PER for responder rate and seizure freedom. Lower adverse events were observed with high dose BRV compared to high dose ESL or PER, but no difference was found in withdrawing because of adverse events. CONCLUSIONS: Indirect comparisons do not demonstrate a significant difference in efficacy between add-on BRV and LCM, ESL, or PER in focal epilepsy, and might suggest a better tolerability of BRV than ESL, and possibly also PER, at the highest effective recommended dose.
BACKGROUND:Brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) have been recently marketed as adjunctive treatments for focal onset seizures. To date, no randomized controlled trial (RCT) has directly compared BRV with ESL, LCM, or PER. PURPOSE: To compare BRV with the other add-on AEDs in patients with uncontrolled focal epilepsy, estimating their efficacy and tolerability through an adjusted, common-reference based indirect comparison meta-analysis. METHODS: We systematically searched RCTs in which add-on treatment with ESL or LCM in patients with focal onset seizures have been compared with placebo. Efficacy and tolerability outcomes were considered. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy of BRV, LCM, ESL, or PER versus placebo. Adjusted indirect comparisons were then made between BRV and the other three AEDs using the obtained results, comparing the minimum and the highest effective recommended daily dose of each drug. RESULTS: Seventeen RCTs, with a total of 4971 patients were included. After adjusting for dose-effects, indirect comparisons showed no difference between BRV and LCM, ESL, or PER for responder rate and seizure freedom. Lower adverse events were observed with high dose BRV compared to high dose ESL or PER, but no difference was found in withdrawing because of adverse events. CONCLUSIONS: Indirect comparisons do not demonstrate a significant difference in efficacy between add-on BRV and LCM, ESL, or PER in focal epilepsy, and might suggest a better tolerability of BRV than ESL, and possibly also PER, at the highest effective recommended dose.
Authors: Susana Ferrao Santos; Anna C Jansen; Lieven Lagae; Benjamin Legros; Sarah Weckhuysen; Paul Boon Journal: Acta Neurol Belg Date: 2020-10-13 Impact factor: 2.396
Authors: Richard P Gale; Ian Pearce; Nicole Eter; Faruque Ghanchi; Frank G Holz; Steffen Schmitz-Valckenberg; Konstantinos Balaskas; Ben J L Burton; Susan M Downes; Haralabos Eleftheriadis; Sheena George; David Gilmour; Robin Hamilton; Andrew J Lotery; Nishal Patel; Priya Prakash; Cynthia Santiago; Saju Thomas; Deepali Varma; Gavin Walters; Michael Williams; Armin Wolf; Rosina H Zakri; Franklin Igwe; Filis Ayan Journal: Br J Ophthalmol Date: 2019-08-05 Impact factor: 4.638