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Multicenter Study
. 2023 Nov 1;80(11):1174-1181.
doi: 10.1001/jamaneurol.2023.3400.

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

Emanuele Cerulli Irelli  1 , Enrico Cocchi  2 , Alessandra Morano  1 , Joanna Gesche  3   4 , Roberto H Caraballo  5 , Simona Lattanzi  6 , Gionata Strigaro  7 , Cecilia Catania  1 , Edoardo Ferlazzo  8   9 , Angelo Pascarella  8   9 , Sara Casciato  10 , Pierpaolo Quarato  10 , Chiara Pizzanelli  11 , Patrizia Pulitano  1 , Loretta Giuliano  12 , Veronica Viola  13 , Barbara Mostacci  13 , Francesco Fortunato  14 , Carla Marini  15 , Giancarlo Di Gennaro  10 , Antonio Gambardella  14 , Angelo Labate  16 , Francesca F Operto  17 , Anna T Giallonardo  1 , Betul Baykan  18 , Christoph P Beier  3   4 , Carlo Di Bonaventura  1 ; Women With Epilepsy Treatment Options and Research (WETOR) Study Group
Collaborators, Affiliations
Multicenter Study

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

Emanuele Cerulli Irelli et al. JAMA Neurol. .

Abstract

Importance: After 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.

Objective: To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE.

Design, setting, and participants: This 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.

Exposures: Levetiracetam or lamotrigine as initial monotherapy.

Main outcomes and measures: Inverse 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.

Results: A 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 < .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 relevance: Results 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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Strigaro reported receiving personal fees from Eisai and Angelini outside the submitted work. Dr Mostacci reported receiving personal fees from Eisai, Angelini Pharma, and Sanofi outside the submitted work; and being an investigator in a trial for which her institution receives a compensation from LivaNova. Dr Beier reported receiving speakers fees from UCB A/S and Eisai and speakers fees and travel support from Arvelle outside the submitted work. Dr Di Bonaventura reported receiving personal fees from UCB Pharma, Eisai, GW Pharmaceuticals, Angelini Pharma, Lusofarmaco, and Ecupharma outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Treatment Failure for Any Reason
Survival curves for treatment failure due to ineffectiveness and adverse effects. ASM indicates antiseizure medication.
Figure 2.
Figure 2.. Treatment Failure for Ineffectiveness Only and Antiseizure Medication (ASM) Retention
A, Survival curves for treatment failure due to ineffectiveness only. B, Survival curves for ASM withdrawal due to both ineffectiveness and adverse effects. C, Survival curves for ASM withdrawal due to adverse effects only.
Figure 3.
Figure 3.. Treatment Failure Across Different Idiopathic Generalized Epilepsy Syndromes
Shown are the survival curves for absence epilepsy (A), juvenile myoclonic epilepsy (B), and epilepsy with generalized tonic-clonic seizures alone (C).
See this image and copyright information in PMC

Comment in

References

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