medwireNews: Levetiracetam may be a better option than lamotrigine for first-line treatment of juvenile myoclonic epilepsy (JME) in women of childbearing age, suggest study findings.
The results are based on a retrospective cohort study comparing levetiracetam and lamotrigine as an alternative monotherapy to valproate for the first-line treatment of idiopathic generalized epilepsy (IGE) in women of reproductive age.
Levetiracetam was found to be superior to lamotrigine for the primary outcome of time to treatment failure. However, when the IGE syndromes – JME (n=259), absence epilepsy (n=109) and epilepsy with generalized tonic–clonic seizures alone (n=175) – were assessed independently the two treatments were comparable for all but JME.
Carlo Di Bonaventura (Sapienza University, Rome, Italy) and colleagues note that, until recently, valproate has “been considered the most effective ASM [anti-seizure medication] in IGE, based on its effectiveness in all generalized seizure types.” However, regulatory bodies now advise against its use in women of child-bearing age, due to “the increased risk of major congenital malformations and neurodevelopmental disorders in offspring exposed to [valproate] in utero.”
Their study involved 543 women diagnosed with IGE according to the International League Against Epilepsy (2022) criteria, of whom 57.5% were prescribed levetiracetam (mean initial maintenance dose of 1197 mg) and 42.5% lamotrigine (219 mg) at a median age of 17 years (range 14–20 years).
During a median 5 years of follow-up, 114 patients taking levetiracetam had a treatment failure event (defined as a medication change due to lack of efficacy or adverse events (AEs), or the addition of a second ASM), compared with 117 of those taking lamotrigine. This equated to a significantly reduced risk with levetiracetam versus lamotrigine, at a hazard ratio for treatment failure of 0.77 after adjusting for baseline variables.
The researchers also found that treatment failure due to lack of effectiveness alone occurred in 95 of the levetiracetam-treated patients, which was significantly fewer than the 104 lamotrigine-treated patients. But other secondary outcomes, including ASM retention (withdrawal due to AEs or lack of effectiveness) and withdrawal due to AEs alone, showed no significant difference between the two groups.
Bonaventura and colleagues highlight, however, that after stratifying results according to IGE syndrome, the superior efficacy and a higher ASM retention with levetiracetam were confirmed only in the patients with JME (62% taking levetiracetam).
The 162 patients in this group who were taking the drug were a significant 53% and 43% less likely than their 97 counterparts taking lamotrigine to have a treatment failure event or stop treatment due to ineffectiveness or AEs, respectively.
Sensitivity analysis confirmed the primary outcome and indicated that patients had a 68% greater likelihood of being free of seizures at 12 months with levetiracetam than lamotrigine treatment, although the researchers caution that this finding was largely driven by the “remarkable superiority of levetiracetam observed among female patients with JME.” There were also fewer instances of worsening myoclonic seizures in the levetiracetam group than the lamotrigine group (0.6% vs 3.3%).
Both ASMs were well tolerated and retention rates were similar, but the rate of AEs was higher in the levetiracetam than the lamotrigine group, at 28.2% versus 18.1%, most notably behavioral effects (16.0 vs 1.0%) and drowsiness (12.2 vs 2.9%), whereas dermatologic AEs were less frequent with levetiracetam than lamotrigine (0.4 vs 6.4%).
The researchers conclude that their data suggest the use of levetiracetam as an alternative ASM medication in women with JME, but that “further studies are warranted to investigate the comparative effectiveness and safety of [valproate] alternatives in IGS syndromes other than JME in female patients of childrearing age.”
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