Clinical comparability of the new antiepileptic drugs in refractory partial epilepsy: A systematic review and meta-analysis

Abstract

SUMMARYPurpose: Evaluate the clinical comparability of new antiepileptic drugs (AEDs) in partial refractory epilepsy. Methods: Systematic review of randomized trials (RCTs) comparing a new AED (add-on treatment) with placebo or another AED. Primary outcomes: responder ( ‡50% seizure reduction) and withdrawal (tolerability) rates. Pooled estimates of odds ratios (ORs) and number needed treat/harm (NNT/NNH) taking into account baseline risk were derived by random-effects meta-analysis. Adjusted frequentist indirect comparisons between AEDs were estimated. Key Findings: Sixty-two placebo-controlled (12,902 patients) and eight head-to-head RCTs (1,370 patients) were included. Pooled ORs for responder and withdrawal rates (vs. placebo) were 3.00 [95% confidence interval (CI) 2.63-3.41] and 1.48 (1.30-1.68), respectively. Indirect comparisons of responder rate based on relative measurements of treatment effect (ORs) favored topiramate (1.52; 1.06-2.20) in comparison to all other AEDs, whereas gabapentin (0.67; 0.46-0.97) and lacosamide (0.66; 0.48-0.92) were less efficacious, without significant heterogeneity. When analyses were based on absolute estimates (NNTs), topiramate and levetiracetam were more efficacious, whereas gabapentin and tiagabine were less efficacious. Withdrawal rate was higher with oxcarbazepine (OR 1.60; 1.12-2.29) and topiramate (OR 1.68; 1.07-2.63), and lower with gabapentin (OR 0.65; 0.42-1.00) and levetiracetam (OR 0.62; 0.43-0.89). Significance: The differences found are of relatively small magnitude to allow a definitive conclusion about which new AED(s) has superior effectiveness. This uncertainty probably reflects the limitations of conclusions based on indirect evidence. The process of pharmacologic clinical decision making in partial refractory epilepsy probably depends more on other aspects, such as individual patient characteristics and pharmacoeconomics, than on available controlled randomized evidence.

Consumption patterns of antiepileptic drugs among epileptic patients in the Western Málaga district

“…Other authors, however, have presented similar findings. 12,13 In our opinion, the most noteworthy finding from this study is that it does not identify fewer adverse events for new drugs than for classic drugs. It does show different ranges of adverse events for each of the two drug types, and this finding is consistent with results from other studies.…”

The efficacy and safety of brivaracetam at different doses for partial-onset epilepsy: a meta-analysis of placebo-controlled studies

“…AEDs have a better effect than placebo in the treatment of partial-onset epilepsy [28]. The analysis by Gao et al [16].…”

The use of recently approved antiepileptic drugs: use with caution, use in refractory patients or use as first-line indications?

“…The efficacy of newer antiepileptic drugs has been proven by the results of several randomized, double-blind, placebo-controlled, add-on trials carried out in patients with drug-resistant epilepsy and confirmed by systematic reviews and meta-analyses [27][28][29][30][31][32][33][34][35]. In these studies, the increased chance of a 50% or greater reduction in seizure frequency compared with placebo ranged from 2.0 (lacosamide) to 4.3 (topiramate) ( Table 4), but the probability of seizure freedom was very low (pooled estimate 2%) as no greater than 6.5% of cases (levetiracetam) were reported to be seizure-free during the course of the study.…”

“…In these trials, common adverse events were reported most frequently among patients receiving active treatment (Table 5). Discontinuation rates for adverse events ranged from 3 to 26% of cases depending on drug and daily dose [27] (also see Table 4). In addition, specific adverse events are predominant with some compounds, including psychosis (vigabatrin), depressive symptoms (zonisamide), affective disorders (levetiracetam) and cognitive impairment (topiramate, retigabine and zonisamide).…”