Authors :
First Author: Hesheng Zhang, MD – Neurology Department, West China Hospital of Sichuan University
Presenting Author: Dong Zhou, MD – Department of Neurology, West China hospital of Sichuan Univeristy
Enhui Zhang, MD – Neurology Department, West China Hospital of Sichuan University; Zhujing Ou, MD – Neurology Department, West China Hospital of Sichuan University; Wenyu Liu, MD – Neurology Department, West China Hospital of Sichuan University; Yujie Chen, MD – Neurology Department, West China Hospital of Sichuan University; Yutong Liu, MS – Ignis Therapeutics (Shanghai) Limited, Shanghai, 200000, People's Republic of China; Hui Ye, MS – Ignis Therapeutics (Shanghai) Limited, Shanghai, 200000, People's Republic of China; Dong Zhou, MD – Neurology Department, West China Hospital of Sichuan University; Xintong Wu, MD – Neurology Department, West China Hospital of Sichuan University
Rationale: Epilepsy is one of the most common neurological disorders, affecting approximately 70 million people, with 50% of patients unable to achieve seizure freedom with monotherapy. Several novel antiseizure medications (ASMs) have been approved in recent years, however, comparative efficacy and safety profile of new and traditional ASMs are limited. Hence, we evaluated the comparative efficacy and safety of all approved add-on ASMs for the treatment of focal epilepsy using network meta-analysis
Methods: An extensive literature search was performed in PubMed, EMBASE, Cochrane and clinical trail.gov databases using predefined search terms from inception through March 2023. The study was performed in accordance with PRISMA guidelines (
CRD42023403450). The study included double blind RCTs in adult patients with focal epilepsy who received add-on antiepileptic treatment with approved ASMs. The outcomes assessed were ≥50% and 100% responder rate, all cause dropout and overall treatment emergent AEs (TEAEs). “Gemtc” 4.0.4 package was used to perform Bayesian analyses. Efficacy outcomes were reported as odds ratio (OR) and 95% confidence interval (CI) while safety as relative risk (RR) and 95% CI.
Results: Literature search retrieved 5807 studies, of which 76 were included in the analysis. All
ASMs showed significantly higher
≥50% responder rate compared to placebo (Figure 1a). Among ASMs
, significantly lower
≥50% responder rate was observed with brivaracetam compared to gabapentin (0.65; 95%CI: 0.41-0.99); pregabalin (0.64; 95%CI: 0.44-0.99); and tiagabine (0.56; 95%CI: 0.31-0.98); perampanel compared to pregabalin (0.63; 95%CI: 0.43-0.92); and tiagabine (0.55; 95%CI: 0.31-0.94). Except rufinamide (2.19; 95%CI: 0.54-10.72), all the included ASMs
showed statistically significant increase in 100% responder rate compared to placebo (figure 1b). Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (8.64; 95%CI: 1.33-243.9); rufinamide (11.68, 95%CI: 1.17-398.7); and zonisamide (8.82; 95CI: 1.00-287.8). Except cenobamate (1.52, 95% CI: 0.92-2.71) and levetiracetam (1.21, 95% CI: 1.0-1.49), all other ASMs
showed significantly increased risk of all cause dropout compared to placebo (Figure 2). None of the ASMs, except brivaracetam (2.13, 95% CI: 1.45-3.43) showed statistically significant increased risk of incidence of overall TEAEs compared to placebo. Fixed effect model was used for all outcomes as the
I2 value was < 50%, except for overall TEAEs where random effect model was used