Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis

Stevelink, Remi; Al-Toma, Dania; Jansen, Floor E.; Lamberink, Herm J.; Asadi-Pooya, Ali A.; Farazdaghi, Mohsen; Cação, Gonçalo; Jayalakshmi, Sita; Patil, Anuja; Özkara, Çiğdem; Aydın, Şenay; Gesche, Joanna; Beier, Christoph P.; Stephen, Linda J.; Brodie, Martin J.; Unnithan, Gopeekrishnan; Radhakrishnan, Ashalatha; Höfler, Julia; Trinka, Eugen; Krause, Roland; Irelli, Emanuele Cerulli; Bonaventura, Carlo Di; Szaflarski, Jerzy P.; Hernández-Vanegas, Laura E.; Moya-Alfaro, Monica L.; Zhang, Yingying; Zhou, Dong; Pietrafusa, Nicola; Specchio, Nicola; Japaridze, Giorgi; Beniczky, Sándor; Janmohamed, Mubeen; Kwan, Patrick; Syvertsen, Marte; Selmer, Kaja Kristine; Vorderwülbecke, Bernd J.; Holtkamp, Martin; Viswanathan, Lakshminarayanapuram Gopal; Sinha, Sanjib; Baykan, Betül; Altindag, Ebru; Podewils, Felix von; Schulz, Juliane; Seneviratne, Udaya; Viloria-Alebesque, Alejandro; Karakis, Ioannis; D’Souza, Wendyl; Sander, Josemir W.; Koeleman, Bobby P. C.; Otte, Willem M.; Braun, Kees P.J.

doi:10.1016/j.eclinm.2022.101732

Cited by 21 publications

(20 citation statements)

References 61 publications

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Section: Discussionsupporting

confidence: 79%

“…Moreover, we highlighted for the first time the impact of catamenial seizures on seizure outcome in EEM, similarly to what has been increasingly observed in other GGE syndromes, particularly in JME. [5][6][7] Finally, when comparing the discriminative ability of the logistic regression models, we found a better AUC in females compared to male patients, suggesting that other unmeasured variables could play a role in the development of drug resistance in male EEM patients.…”

Section: Discussionmentioning

confidence: 67%

“…5 The importance of a sex-stratified approach in GGE was further supported by recent results highlighting the prognostic impact of catamenial seizures in JME and other GGE syndromes. [5][6][7] Moreover, the recent limitations introduced by worldwide regulatory agencies for the use of valproate (VPA) in female patients of childbearing potential, and the consequent differences in antiseizure medication (ASM) exposure, once again highlighted the prognostic relevance of sex across different GGE syndromes. 8,9 In this study, by the ongoing EEM Study Group, we aimed to explore the occurrence of electroclinical differences according to sex and investigate the possible existence of sex-specific prognostic determinants in EEM.…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, previous studies in juvenile myoclonic epilepsy (JME) highlighted relevant differences in clinical presentation according to sex, with female patients displaying higher rates of absence seizures, PS, and reflex seizures 5 . The importance of a sex‐stratified approach in GGE was further supported by recent results highlighting the prognostic impact of catamenial seizures in JME and other GGE syndromes 5–7 . Moreover, the recent limitations introduced by worldwide regulatory agencies for the use of valproate (VPA) in female patients of childbearing potential, and the consequent differences in antiseizure medication (ASM) exposure, once again highlighted the prognostic relevance of sex across different GGE syndromes 8,9 …”

Section: Introductionmentioning

confidence: 99%

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Sex‐based electroclinical differences and prognostic factors in epilepsy with eyelid myoclonia

et al. 2023

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex‐based electroclinical differences and prognostic factors in epilepsy with eyelid myoclonia

et al. 2023

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“…Baseline clinical characteristics were computed using nonimputed data. Missing data were handled with multiple imputations with chained equations, imputing both outcome and predictors . The rate of missing data for all variables is shown in the eFigure in Supplement 1.…”

Section: Methodsmentioning

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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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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The pharmacological treatment of epilepsy in adults

Tomson

Zelano

Dang

et al. 2023

Epileptic Disorders

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The pharmacological treatment of epilepsy entails several critical decisions that need to be based on an individual careful risk–benefit analysis. These include when to initiate treatment and with which antiseizure medication (ASM). With more than 25 ASMs on the market, physicians have opportunities to tailor the treatment to individual patients´ needs. ASM selection is primarily based on the patient's type of epilepsy and spectrum of ASM efficacy, but several other factors must be considered. These include age, sex, comorbidities, and concomitant medications to mention the most important. Individual susceptibility to adverse drug effects, ease of use, costs, and personal preferences should also be taken into account. Once an ASM has been selected, the next step is to decide on an individual target maintenance dose and a titration scheme to reach this dose. When the clinical circumstances permit, a slow titration is generally preferred since it is associated with improved tolerability. The maintenance dose is adjusted based on the clinical response aiming at the lowest effective dose. Therapeutic drug monitoring can be of value in efforts to establish the optimal dose. If the first monotherapy fails to control seizures without significant adverse effects, the next step will be to gradually switch to an alternative monotherapy, or sometimes to add another ASM. If an add‐on is considered, combining ASMs with different modes of action is usually recommended. Misdiagnosis of epilepsy, non‐adherence and suboptimal dosing are frequent causes of treatment failure and should be excluded before a patient is regarded as drug‐resistant. Other treatment modalities, including epilepsy surgery, neuromodulation, and dietary therapies, should be considered for truly drug‐resistant patients. After some years of seizure freedom, the question of ASM withdrawal often arises. Although successful in many, withdrawal is also associated with risks and the decision needs to be based on careful risk–benefit analysis.

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Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis

Cited by 21 publications

References 61 publications

Sex‐based electroclinical differences and prognostic factors in epilepsy with eyelid myoclonia

Sex‐based electroclinical differences and prognostic factors in epilepsy with eyelid myoclonia

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

The pharmacological treatment of epilepsy in adults

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