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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

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Abstract

Background

Approximately two-thirds of patients with newly diagnosed epilepsy become seizure-free after antiepileptic drug (AED) treatment. A crucial issue for these patients and their families, especially after a long period of seizure freedom, is when to stop their medications.

Objective

The aim of this study was to identify the optimal timing of AED withdrawal in adults with focal epilepsy who had been seizure-free for ≥ 2 years.

Methods

Adults with focal epilepsy who had been seizure-free for ≥ 2 years were recruited. Based on their decision to discontinue (withdrawal) or continue (non-withdrawal) AED treatment, patients were assigned to withdrawal or non-withdrawal subgroups according to the length of remission (2 to < 3 years, 3 to < 4 years, 4 to < 5 years and ≥ 5 years). The relapse risks of the withdrawal and corresponding non-withdrawal subgroups were compared, and the relative relapse risks were assessed in a Cox proportional hazard regression model.

Results

A total of 213 eligible patients began to withdraw from AED treatment; 70 had been seizure-free for 2 to < 3 years, 62 had been seizure-free for 3 to < 4 years, 37 had been seizure-free for 4 to < 5 years and 44 had been seizure-free for ≥ 5 years. The figures for the corresponding non-withdrawal subgroups were 463, 334, 251 and 182, respectively. There was a significantly higher risk of seizure relapse in patients withdrawing from AEDs after 2 to < 5 years of seizure freedom than in the corresponding non-withdrawal controls, and the relative relapse risk was 3.052 (95% confidence interval [CI] 2.126–4.381; p < 0.001) for the seizure-free period of 2 to < 3 years, 3.617 (95% CI 2.384–5.488; p < 0.001) for 3 to < 4 years and 2.644 (95% CI 1.456–4.799; p = 0.001) for 4 to < 5 years. However, for patients who were seizure-free for ≥ 5 years, AED withdrawal did not significantly increase the risk of seizure relapse compared with that of patients continuing treatment (hazard ratio [HR] 1.362, 95% CI 0.634–2.926, p = 0.428). Compared with a seizure-free period of 2 to < 3 years, the relative relapse risk after AED withdrawal was significantly reduced only after being seizure-free for ≥ 5 years (HR 0.441, 95% CI 0.233–0.834; p = 0.012).

Conclusion

Overall, for adults with focal epilepsy, withdrawal from AEDs significantly increased the risk of seizure relapse after being seizure-free for 2 to < 5 years, but might not increase the risk if the seizure-free period was ≥ 5 years.

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Data Availability

The anonymized datasets generated during the current study are available from the corresponding author upon reasonable request.

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Author notes

  1. Xinshi Wang and Ruqian He contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China

    Xinshi Wang, Rongyuan Zheng, Siqi Ding, Xueying Li, Yingjie Hua, Qingyi Zeng, Niange Xia, Zhenguo Zhu & Huiqin Xu

  2. Department of Neuroscience, The Central Clinical School, Monash University, Melbourne, VIC, Australia

    Xinshi Wang & Patrick Kwan

  3. Department of Neurology, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia

    Xinshi Wang & Patrick Kwan

  4. Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University (Ruian People’s Hospital), Wenzhou, Zhejiang, People’s Republic of China

    Ruqian He

  5. School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China

    Yi Wang

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Contributions

Xinshi Wang: Study concept and design, acquisition of data, statistical analysis, drafting of the manuscript. Ruqian He: Study concept and design, drafting of the manuscript, acquisition of data, analysis and interpretation of data. Rongyuan Zheng: Designing and conceptualizing the study, data acquisition, and revising the manuscript. Yi Wang: Statistical analysis. Siqi Ding, Xueying Li, Yingjie Hua, Qingyi Zeng, Niange Xia and Zhenguo Zhu: Acquisition of data. Patrick Kwan: Study concept, interpretation of data, critical revision of the manuscript for intellectual content. Huiqin Xu: Study supervision, study concept and design, interpretation of data, revision of the manuscript for intellectual content.

Corresponding authors

Correspondence to Patrick Kwan or Huiqin Xu.

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Funding

This research was partly supported by the China Scholarship Council (Grant no. 201808330160, to XW) and the Zhejiang Medical and Health Science and Technology Project (grant no. 2019320104, to XW).

Conflicts of interest

Xinshi Wang has received a grant from the China Scholarship Council (201808330160). Patrick Kwan reports research grants from Biscayne, Eisai, GW Pharmaceuticals, UCB Pharma, LivaNova and Zynerba. He and/or his institution also received speaker’s or consultancy fees from Eisai, LivaNova and UCB Pharma. Huiqin Xu reports speaker’s fees from Novartis and UCB Pharma. Ruqian He, Rongyuan Zheng, Siqi Ding, Yi Wang, Xueying Li, Yingjie Hua, Qingyi Zeng, Niange Xia and Zhenguo Zhu report no disclosures.

Ethical approval

The study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University.

Informed consent

The requirement for written informed consent was waived for all of the participants because our study involved no more than minimal risk and involved no procedures for which written consent is normally required outside of the research context.

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Wang, X., He, R., Zheng, R. et al. 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. CNS Drugs 33, 1121–1132 (2019). https://doi.org/10.1007/s40263-019-00679-3

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  • DOI: https://doi.org/10.1007/s40263-019-00679-3

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