Treatment outcomes in women with idiopathic generalized epilepsy

Kiiski, Rebecca; Basnyat, Pabitra; Raitanen, Jani; Rainesalo, Sirpa; Peltola, Jukka; Mäkinen, Jussi

doi:10.1111/ane.13567

Cited by 3 publications

(5 citation statements)

References 27 publications

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“…Conversely, lamotrigine and levetiracetam have been suggested as possible initial monotherapies by the NICE guidelines and by the ILAE in patients with JAE, considering their high probability of experiencing GTCS along with absences . In addition, it is worth underscoring that levetiracetam and lamotrigine have been repeatedly found as the safest ASMs to be prescribed during pregnancy, whereas teratogenic issues have been raised with ethosuximide, and its effects on offspring have not been sufficiently investigated . For this reason, we avoided including ethosuximide in our study, and we purposefully focused on the comparative effectiveness of levetiracetam and lamotrigine.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, multiple reports showed the possible increased chance of uncontrolled seizures in female patients with IGE who are not prescribed VPA and highlighted the challenging treatment of these patients . Despite the relevance of this topic and the female preponderance observed in IGE, no study, to our knowledge, has specifically investigated the most effective ASM alternatives to VPA in a target group of female individuals of childbearing age, and available evidence is mainly based on monocentric studies and case series …”

Section: Introductionmentioning

confidence: 99%

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Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy

Cerulli Irelli,

Cocchi,

Morano

et al. 2023

JAMA Neurol

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ImportanceAfter the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors’ knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients.ObjectiveTo compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE.Design, Setting, and ParticipantsThis was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription.ExposuresLevetiracetam or lamotrigine as initial monotherapy.Main Outcomes and MeasuresInverse probability of treatment weighting (IPTW)–adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy.ResultsA total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P &lt; .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60).Conclusions and RelevanceResults of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy

Cerulli Irelli,

Cocchi,

Morano

et al. 2023

JAMA Neurol

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“…1,5 Treatment of IGE relies on using broad-spectrum antiseizure medications (ASMs), and valproate (VPA) has long been considered the first-choice treatment in this setting, because of its yet unsurpassed efficacy. 6,7 However, the use of VPA in women of childbearing age is limited due to its teratogenic effects, and its negative neurodevelopmental effects on in utero exposed children. [6][7][8] Moreover, in men, VPA can have detrimental effects on sperm quality and testicular function/volume and may cause infertility.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 However, the use of VPA in women of childbearing age is limited due to its teratogenic effects, and its negative neurodevelopmental effects on in utero exposed children. [6][7][8] Moreover, in men, VPA can have detrimental effects on sperm quality and testicular function/volume and may cause infertility. 9,10 Although the prognosis for IGE is more favorable than for some other epilepsies, up to 15% of individuals with IGE remain refractory to treatment.…”

Section: Introductionmentioning

confidence: 99%

“…IGEs are also characterized by an electroencephalogram profile that includes normal background activity with generalized spike–wave and/or polyspike–wave discharges, which may be activated by hyperventilation and photic stimulation 1,5 . Treatment of IGE relies on using broad‐spectrum antiseizure medications (ASMs), and valproate (VPA) has long been considered the first‐choice treatment in this setting, because of its yet unsurpassed efficacy 6,7 . However, the use of VPA in women of childbearing age is limited due to its teratogenic effects, and its negative neurodevelopmental effects on in utero exposed children 6–8 .…”

Section: Introductionmentioning

confidence: 99%

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Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice

Trinka

Alsaadi²,

Goji

et al. 2023

Epilepsia

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ObjectiveThis study was undertaken to evaluate perampanel (PER) when used under real‐world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study.MethodsThe multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic–clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation.ResultsThe Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months.SignificanceThis subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad‐spectrum antiseizure medication for the treatment of IGE.

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