Relative Seizure Relapse Risks Associated with Antiepileptic Drug Withdrawal After Different Seizure-Free Periods in Adults with Focal Epilepsy: A Prospective, Controlled Follow-Up Study

Wang, Xinshi; He, Ruqian; Zheng, Ran; Ding, Siqi; Wang, Yi; Li, Xueying; Hua, Yingjie; Zeng, Qian; Zhu, Zhenguo; Kwan, Patrick; Xu, Huiqin

doi:10.1007/s40263-019-00679-3

Cited by 13 publications

(9 citation statements)

References 37 publications

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“…However, subgroup analyses revealed that the relative risk of seizure recurrence decreased with the length of seizure remission before ASM withdrawal. Consistently, Wang et al compared the risk of seizure recurrence according to the length of remission before ASM withdrawal [ 45 ]. While the recurrence risk was significantly elevated after a remission phase of two years, there was no difference in the risk for patients who had been seizure-free for five or more years of remission.…”

Section: Resultsmentioning

confidence: 99%

The sense of stopping migraine prophylaxis

et al. 2023

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Introduction Migraine prophylactic therapy has changed over recent years with the development and approval of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. As new therapies emerged, leading headache societies have been providing guidelines on the initiation and escalation of such therapies. However, there is a lack of robust evidence looking at the duration of successful prophylaxis and the effects of therapy discontinuation. In this narrative review we explore both the biological and clinical rationale for prophylactic therapy discontinuation to provide a basis for clinical decision-making. Methods Three different literature search strategies were conducted for this narrative review. These include i) stopping rules in comorbidities of migraine in which overlapping preventives are prescribed, notably depression and epilepsy; ii) stopping rules of oral treatment and botox; iii) stopping rules of antibodies targeting the CGRP (receptor). Keywords were utilized in the following databases: Embase, Medline ALL, Web of Science Core collection, Cochran Central Register of Controlled Trials, and Google Scholar. Discussion Reasons to guide decision-making in stopping prophylactic migraine therapies include adverse events, efficacy failure, drug holiday following long-term administration, and patient-specific reasons. Certain guidelines contain both positive and negative stopping rules. Following withdrawal of migraine prophylaxis, migraine burden may return to pre-treatment level, remain unchanged, or lie somewhere in-between. The current suggestion to discontinue CGRP(-receptor) targeted mAbs after 6 to 12 months is based on expert opinion, as opposed to robust scientific evidence. Current guidelines advise the clinician to assess the success of CGRP(-receptor) targeted mAbs after three months. Based on excellent tolerability data and the absence of scientific data, we propose if no other reasons apply, to stop the use of mAbs when the number of migraine days decreases to four or fewer migraine days per month. There is a higher likelihood of developing side effects with oral migraine preventatives, and so we suggest stopping these drugs according to the national guidelines if they are well tolerated. Conclusion Translational and basic studies are warranted to investigate the long-term effects of a preventive drug after its discontinuation, starting from what is known about the biology of migraine. In addition, observational studies and, eventually, clinical trials focusing on the effect of discontinuation of migraine prophylactic therapies, are essential to substantiate evidence-based recommendations on stopping rules for both oral preventives and CGRP(-receptor) targeted therapies in migraine. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

The sense of stopping migraine prophylaxis

et al. 2023

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“…It had been reported that the possibility of SF after ASM withdrawal was about 60% in the general population with focal epilepsy, who had been seizure-free longer than 5 years. 37 Our data showed that the chance of SF after ASM withdrawal was very slim for epileptic patients with MCD. Therefore, the clinician may need to be very cautious in reducing the ASM dosage in epileptic patients with MCD, especially after achieving SF.…”

Section: Discussionmentioning

confidence: 59%

Response to antiseizure medications in epileptic patients with malformation of cortical development

Chen

Jin

Aung

et al. 2021

Ther Adv Neurol Disord

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Background: Malformation of cortical development (MCD) is one of the most common causes of pharmacoresistant epilepsy. Improving the knowledge of antiseizure medications (ASMs) treatment response in epileptic patients with MCD is crucial for optimal treatment options, either pharmacological therapy or non-pharmacological intervention. Aim: To investigate the patterns of medical treatment outcome and the predictors for seizure freedom (SF) with ASM regimens in epilepsy caused by MCD. Methods: The epileptic patients with MCD were consecutively enrolled from March 2013 to June 2019. SF was defined as no seizures for at least 12 months or three times the longest pretreatment inter-seizure interval, whichever was longer. Outcomes were classified into three patterns: pattern A: patients achieved SF at one point and remained so throughout follow-up; pattern B: patients’ seizures fluctuated between periods of SF and relapse; pattern C: SF never attained. The terminal SF was defined if the patients remained SF at the last follow-up visit. Results: A total of 164 epileptic patients with MCD were included. Pattern A was observed in 22, pattern B in 42, and pattern C in 100 patients. SF was ever achieved in 64 (pattern A and B) patients. Twenty-nine patients had terminal SF after a median follow-up time of 4.3 years. With continuing ASM treatment, seizure relapse risk was very low after a 5-year seizure-free period. The pretreatment seizure frequency was the only independent predictor for pattern A and seizure relapse. Sodium channel blockers monotherapy (33.8%) was more effective than levetiracetam (4.5%) in rendering SF in the initial ASM regimen. Conclusion: Medical treatment can be successful in a minority of epileptic patients with MCD, and pretreatment seizure frequency helps to predict the treatment outcome. An unequal efficacy of ASMs in epilepsy caused by MCD suggests etiological evaluation is vital in the management of focal epilepsy.

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“…This result is coherent with some previous reports, 1 , 14 , 27 whereas others showed either different cut‐offs (5 or 3 years) or progressive reduction of risk without giving any definite cut‐off value. 2 , 24 , 31 Therefore, until more evidence is gathered, it seems important that future studies include patients with different duration of seizure‐free period on therapy.…”

Section: Discussionmentioning

confidence: 99%

“…The following clinical-demographic characteristics were recorded: sex, age at seizure onset (stratified according to Lamberink et al 2 ), duration of epilepsy (from the first to the last seizure), family history of epilepsy, neonatal seizures (until the first month of life), febrile seizures in childhood, number of seizures before AED discontinuation (<10 or ≥10), 2 duration of the seizure-free period on therapy (from the last seizure attack to AED withdrawal; variable was recorded both categorized according to Wang et al 24 and continuous), number of discontinued drugs, seizure type (focal/generalized), etiology of epilepsy (structural, assessed by magnetic resonance imaging [MRI]; genetic; unknown), diagnosis of a self-limiting epilepsy syndrome (eg, absence epilepsy, benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome), developmental delay (assessed only by clinical judgment and history of need for specialized schooling, as in 3/10 of the papers included in the meta-analysis of Lamberink et al 2 ), electroencephalography (EEG) epileptiform abnormalities before discontinuation, age at last seizure, age at AED withdrawal, plasma levels of AEDs at the beginning of withdrawal (within, below, or above therapeutic range), persistent motor deficits, psychiatric disorders for which the patient assumed a specific drug, failure of previous AED discontinuations, duration of AED tapering (0-3 months; 4-12 months; more than 1 year), epileptiform abnormalities on EEG during or at the end of AED withdrawal, epileptic encephalopathy, and presence of juvenile myoclonic epilepsy. For LPM validation in this patient cohort, the 2-and 5year seizure recurrence probability for each patient was estimated using the web-based tool developed by the authors (http://epile psypr edict ionto ols.info).…”

Section: Clinical-demographic Characteristics Analyzedmentioning

confidence: 99%

Prediction of seizure recurrence risk following discontinuation of antiepileptic drugs

et al. 2021

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Objective Discontinuation of antiepileptic drugs (AEDs) in seizure‐free patients is an important goal because of possible long‐term side effects and the social stigma burden of epilepsy. The purpose of this work was to assess seizure recurrence risk after suspension of AEDs, to evaluate predictors for recurrence, and to investigate the recovery of seizure control after relapse. In addition, the accuracy of a previously published prediction model of seizure recurrence risk was estimated. Methods Seizure‐free patients with epilepsy who had discontinued AEDs were retrospectively enrolled. The frequency of seizure relapses after AED withdrawal as well as prognosis after recurrence were assessed and the predictive role of baseline clinical‐demographic variables was evaluated. The aforementioned prediction model was also validated and its accuracy assessed at different seizure‐relapse probability levels. Results The enrolled patients (n = 133) had been followed for a median of 3 years (range 0.8–33 years) after AED discontinuation; 60 (45%) of them relapsed. Previous febrile seizures in childhood (hazard ratio [HR] 3.927; 95% confidence interval [CI] 1.403–10.988), a seizure‐free period on therapy of less than 2 years (HR 2.313; 95% CI 1.193–4.486), and persistent motor deficits (HR 4.568; 95% CI 1.412–14.772) were the clinical features associated with relapse risk in univariate analysis. Among these variables, only a seizure‐free period on therapy of less than 2 years was associated with seizure recurrence in multivariate analysis (HR 2.365; 95% CI 1.178–4.7444). Pharmacological control of epilepsy was restored in 82.4% of the patients who relapsed. In this population, the aforementioned prediction model showed an unsatisfactory accuracy. Significance A period of freedom from seizure on therapy of less than 2 years was the main predictor of seizure recurrence. The accuracy of the previously described prediction tool was low in this cohort, thus suggesting its cautious use in real‐world clinical practice.

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Relative Seizure Relapse Risks Associated with Antiepileptic Drug Withdrawal After Different Seizure-Free Periods in Adults with Focal Epilepsy: A Prospective, Controlled Follow-Up Study

Cited by 13 publications

References 37 publications

The sense of stopping migraine prophylaxis

The sense of stopping migraine prophylaxis

Response to antiseizure medications in epileptic patients with malformation of cortical development

Prediction of seizure recurrence risk following discontinuation of antiepileptic drugs

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