Lacosamid versus brivaracetam jako leki wspomagające w leczeniu opornej na leki ogniskowej epilepsji: porównanie pośrednie zakotwiczone na placebo i metaanaliza sieciowa

PURPOSE: Previous multi-drug network meta-analyses have emphasized overall rankings of newer antiseizure medications, but whether current randomized evidence can distinguish between lacosamide (LCM) and brivaracetam (BRV) in adults with drug-resistant focal epilepsy remains unclear. We therefore conducted a placebo-anchored indirect comparison and network meta-analysis. METHODS: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus from inception to 15 January 2026 for double-blind, placebo-controlled randomized trials of adjunctive LCM or BRV in patients aged ≥ 16 years with drug-resistant focal epilepsy. Outcomes were extracted from the maintenance period or the closest comparable fixed-dose period. Relative effects were summarized as risk ratios (RRs) with 95% confidence intervals (CIs), comparing LCM with BRV. A random-effects network meta-analysis using placebo as the common comparator was performed alongside an anchored Bucher indirect comparison. Exploratory Asian subgroup and dose-aligned analyses were performed, and certainty of evidence was assessed using CINeMA. RESULTS: Eight trials contributed 3338 participants to the primary ≥ 50% responder analysis. In the overall population, LCM did not differ clearly from BRV for the ≥ 50% responder rate (RR 0.96, 95% CI 0.72-1.27) or seizure freedom (RR 0.41, 95% CI 0.09-1.81). Treatment-emergent adverse events were similar (RR 0.97, 95% CI 0.86-1.10). Serious adverse events were numerically higher with LCM but imprecise (RR 2.08, 95% CI 0.93-4.64), and discontinuation due to adverse events was also imprecise (RR 1.57, 95% CI 0.76-3.21). Exploratory Asian subgroup and dose-aligned analyses showed no clear efficacy separation but were limited by sparse events and imprecision. CINeMA ratings indicated generally low certainty for the principal indirect comparisons, mainly because of imprecision and transitivity concerns. CONCLUSION: In adults with drug-resistant focal epilepsy, placebo-anchored indirect evidence did not show a clear difference in short-term efficacy between adjunctive LCM and BRV. Estimates for selected tolerability outcomes were imprecise and based on low-certainty, fully indirect evidence. These findings do not establish a definitive comparative advantage of either treatment, and direct comparative studies are needed.