Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis

Abstract

Second and third generation AEDs have been directly compared to controlled-release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal epilepsy. Conversely, no head-to-head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta-analysis (NMA). Randomized, double-blinded, parallel group, monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed untreated epilepsy with focal-onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12 months, the occurrence of treatment-emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6- and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659, 95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ-CR.

Long‐term safety and efficacy of lacosamide and controlled‐release carbamazepine monotherapy in patients with newly diagnosed epilepsy

“…10,[12][13][14] These trials showed that levetiracetam, zonisamide, lacosamide, and eslicarbazepine were noninferior to carbamazepine-CR, and provided class I evidence of efficacy in adults with focal epilepsy that led to approval of these drugs as monotherapy options in Europe. 15 In the lacosamide extension trial, most patients on lacosamide and carbamazepine-CR remained at the lowest dose level, similar to what was observed in the initial trial. 15 However, lacosamide was associated with a significantly lower incidence of discontinuations due to TEAEs than carbamazepine-CR.…”

“…10,[12][13][14] A recent network meta-analysis of these noninferiority trials compared the efficacy and tolerability of these AED monotherapies and found no statistical differences in the 6-and 12-month seizure freedom and incidence of TEAEs between levetiracetam, zonisamide, lacosamide, eslicarbazepine, and carbamazepine-CR. 15 However, lacosamide was associated with a significantly lower incidence of discontinuations due to TEAEs than carbamazepine-CR. 15 In the lacosamide extension trial, most patients on lacosamide and carbamazepine-CR remained at the lowest dose level, similar to what was observed in the initial trial.…”

“…15 However, lacosamide was associated with a significantly lower incidence of discontinuations due to TEAEs than carbamazepine-CR. 15 In the lacosamide extension trial, most patients on lacosamide and carbamazepine-CR remained at the lowest dose level, similar to what was observed in the initial trial. 10 The most commonly reported TEAEs with lacosamide were nasopharyngitis, headache, and dizziness, in line with those reported previously.…”

Antiepileptic drug monotherapy for epilepsy in the elderly: A systematic review and network meta‐analysis

“…NMAs are not substitutes for clinical trials directly comparing two or more drugs, but they may offer reliable evidence of the relative efficacy and safety, 20,26 provide useful information about the hierarchy of competing interventions, and represent a complementary guide to inform physicians in their clinical decision-making. Although no significant difference in efficacy was found across treatments, LCM, LTG, and LEV had the highest probability of ranking best for achieving seizure freedom.…”

“…Although no significant difference in efficacy was found across treatments, LCM, LTG, and LEV had the highest probability of ranking best for achieving seizure freedom. NMAs are not substitutes for clinical trials directly comparing two or more drugs, but they may offer reliable evidence of the relative efficacy and safety, 20,26 provide useful information about the hierarchy of competing interventions, and represent a complementary guide to inform physicians in their clinical decision-making.…”