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Treatment Outcomes of Newly Diagnosed Epilepsy: A Systematic Review and Meta-analysis

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Abstract

Background and Objectives

Understanding the multi-faceted treatment outcomes of newly diagnosed epilepsy is critical for developing rational therapeutic strategies. A meta-analysis was conducted to derive pooled estimates of a range of seizure outcomes in children and adults with newly diagnosed epilepsy commenced on antiseizure medication treatment, and to identify factors associated with different outcomes.

Methods

PubMed/EMBASE were screened for eligible articles between 1 January, 1995 and 1 May, 2021 to include unselected cohort studies with a ≥ 12-month follow-up of seizure outcomes. Proportions of patients seizure free at different follow-up timepoints and their characteristics at the study population level were extracted. The patients were group-wise aggregated using a random-effects model. Primary outcomes were proportions of patients with cumulative 1-year seizure freedom (C1YSF), and 1-year and 5-year terminal seizure freedom (T1YSF and T5YSF). Secondary outcomes included the proportions of patients with early sustained seizure freedom, drug-resistant epilepsy and seizure-free off antiseizure medication at the last follow-up (off antiseizure medications). A separate random-effects meta-analysis was performed for nine predictors of importance.

Results

In total, 39 cohorts (total n = 21,139) met eligibility criteria. They included 15 predominantly adult cohorts (n = 12,024), 19 children (n = 6569), and 5 of mixed-age groups (n = 2546). The pooled C1YSF was 79% (95% confidence interval [CI] 74–83). T1YSF was 68% (95% CI 63–72) and T5YSF was 69% (95% CI 62–75). Children had higher C1YSF (85% vs 68%, p < 0.001) and T1YSF than adult cohorts (74% vs 61%, p = 0.007). For secondary outcomes, 33% (95% CI 27–39) of patients achieved early sustained seizure freedom, 17% (95% CI 13–21) developed drug resistance, and 39% (95% CI 30–50) were off antiseizure medications at the last follow-up. Studies with a longer follow-up duration correlated with higher C1YSF (p < 0.001) and being off antiseizure medications (p = 0.045). Outcomes were not associated with study design (prospective vs retrospective), cohort size, publication year, or the earliest date of recruitment. Predictors of importance in newly diagnosed epilepsy include etiology, epilepsy type, abnormal diagnostics (neuroimaging, examination, and electroencephalogram findings), number of seizure types, and pre-treatment seizure burden.

Conclusions

Seizure freedom is achieved with currently available antiseizure medications in most patients with newly diagnosed epilepsy, yet this is often not immediate, may not be sustainable, and has not improved over recent decades. Symptomatic etiology, abnormal neuro-diagnostics, and increased pre-treatment seizure burden and seizure types are important predictors for unfavorable outcomes in newly diagnosed epilepsy. The study findings may be used as a quantitative benchmark on the efficacy of future antiseizure medication therapy for this patient population.

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Authors and Affiliations

  1. Department of Neuroscience, Central Clinical School, The Alfred Centre, Monash University, Level 6, 99 Commercial Road, Melbourne, VIC, 3004, Australia

    Mubeen Janmohamed, Haris Hakeem, Suhailah Hakami, Piero Perucca, Terence J. O’Brien, Ana Antonic-Baker, Zhibin Chen & Patrick Kwan

  2. Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia

    Mubeen Janmohamed, Haris Hakeem, Piero Perucca, Terence J. O’Brien & Patrick Kwan

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

    Suyi Ooi, Piero Perucca, Terence J. O’Brien & Patrick Kwan

  4. Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia

    Lily Vu, Piero Perucca, Terence J. O’Brien, Zhibin Chen & Patrick Kwan

  5. Bladin-Berkovic Comprehensive Epilepsy Program, Austin Health, Melbourne, VIC, Australia

    Piero Perucca

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  1. Mubeen Janmohamed
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Correspondence to Mubeen Janmohamed.

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Funding

This study did not receive any specific funding.

Conflicts of Interest/Competing Interests

MJ and HH are supported by the Monash University RTP Stipend scholarship. PP is supported by the National Health and Medical Research Council (APP1163708), the Epilepsy Foundation, The University of Melbourne, Monash University, Brain Australia, the Weary Dunlop Medical Research Foundation, and the Norman Beischer Medical Research Foundation and has received speaker honoraria or consultancy fees to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. TJO is supported by an NHMRC Investigator Grant (APP1176426) and his institution has received research grants, speaker honoraria, or consultancy fees from Chiesi, Eisai, UCB Pharma, Zynerba Pharmaceuticals, ES Pharmaceuticals, Supernus, and LivaNova, outside the submitted work. ZC is supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia (GNT1156444), and he/his institution has received consultancy fees and/or research grants from Arvelle Therapeutics and UCB Pharma. PK is supported by a Medical Research Future Fund Practitioner Fellowship (MRF1136427). He/his institution has received research grants, speaker honoraria, or consultancy fees from Chiesi, Eisai, UCB Pharma, and LivaNova, outside the submitted work. The other authors have no disclosures to declare.

Ethics Approval

No ethical approval was required for this study. All data were study-level characteristics and outcomes for a meta-analysis. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines

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Availability of Data and Material

All data extracted have been made available in the online supplementary material. Further cohort data information can be obtained through request to the corresponding author.

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Authors’ Contributions

MJ was the first author involved in the design, systematic search protocol, conceptualization, screening, data extraction, quality rating, statistical contribution, and authoring of the manuscript. HH was involved in the screening, data extraction, quality rating, and editing of the manuscript. SO, LV, and SH were involved in the screening and editing of the manuscript. A-AB was involved in the design, quality rating, and editing of the manuscript. ZC was involved in the design, statistical analysis, and editing of the manuscript. PP and TO were involved in the editing of the manuscript. PK was the senior author in the conceptualizing, design, statistical contribution, and editing of the manuscript.

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Janmohamed, M., Hakeem, H., Ooi, S. et al. Treatment Outcomes of Newly Diagnosed Epilepsy: A Systematic Review and Meta-analysis. CNS Drugs 37, 13–30 (2023). https://doi.org/10.1007/s40263-022-00979-1

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