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Observational Study
. 2018 Mar 1;75(3):279-286.
doi: 10.1001/jamaneurol.2017.3949.

Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study

Zhibin Chen  1   2 , Martin J Brodie  3 , Danny Liew  4 , Patrick Kwan  1   2   5   6
Affiliations
Observational Study

Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study

Zhibin Chen et al. JAMA Neurol. .

Erratum in

  • Error in Data Presentation.
    [No authors listed] [No authors listed] JAMA Neurol. 2018 Mar 1;75(3):384. doi: 10.1001/jamaneurol.2018.0018. JAMA Neurol. 2018. PMID: 29435581 Free PMC article. No abstract available.

Abstract

Importance: A study published in 2000 showed that more than one-third of adults with epilepsy have inadequate control of seizures with antiepileptic drugs (AEDs). This study evaluates overall treatment outcomes in light of the introduction of more than 1 dozen new AEDs in the past 2 decades.

Objective: To assess long-term treatment outcome in patients with newly diagnosed and treated epilepsy.

Design, setting, and participants: This longitudinal observational cohort study was conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. A total of 1795 individuals who were newly treated for epilepsy with AEDs between July 1, 1982, and October 31, 2012, were included in this analysis. All patients were followed up for a minimum of 2 years (until October 31, 2014) or until death, whichever came sooner. Data analysis was completed between March 2015 and May 2016.

Exposures: Treatment with antiepileptic drugs for patients newly diagnosed with epilepsy.

Main outcomes and measures: Seizure control was assessed at the end of the study period. Probability of achieving 1-year seizure freedom was estimated for each AED regimen prescribed. Multivariable models assessed the associations between risk factors and AED treatment outcome after adjustments were made for demographic and clinical characteristics.

Results: Of the 1795 included patients, 964 (53.7%) were male; the median age was 33 years (range, 9-93 years). At the end of the study period, 1144 patients (63.7%) had been seizure free for the previous year or longer. Among those achieving 1-year seizure freedom, 993 (86.8%) were taking monotherapy and 1028 (89.9%) had achieved seizure control with the first or second AED regimens. Of the total patient pool, 906 (50.5%) remained seizure free for 1 year or longer with the initial AED. If this AED failed, the second and third regimens provided an additional 11.6% and 4.4% likelihoods of seizure freedom, respectively. Only 2.12% of patients attained optimal seizure control with subsequent AEDs. Epilepsy that was not successfully controlled with the first AED had 1.73 times greater odds of not responding to treatment for each subsequent medication regimen (odds ratio, 1.73; 95% CI, 1.56-1.91; P < .001).

Conclusions and relevance: Despite the availability of many new AEDs with differing mechanisms of action, overall outcomes in newly diagnosed epilepsy have not improved. Most patients who attain control do so with the first or second AED. The probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried. More than one-third of patients experience epilepsy that remains uncontrolled.

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Conflict of interest statement

Conflict of Interest Disclosures: Outside the submitted work, Dr Brodie serves on the scientific advisory boards of Eisai Ltd, UCB Pharma, GlaxoSmithKline, Lundbeck, Bial, GW Pharmaceuticals, and Takeda; is on the speakers’ bureau for Eisai Ltd, UCB Pharma, GlaxoSmithKline, Lundbeck, Sanofi Aventis, and Abbott; and has accepted travel grants for scientific meetings from Eisai Ltd, UCB Pharma, and Lundbeck. Dr Liew has received research grants from the National Health and Medical Research Council of Australia, the Australian Research Council, and the National Heart Foundation of Australia. He and/or his institution has also received speaker or consultancy fees and/or research grants from Pfizer, AbbVie, Sanofi, AstraZeneca, GlaxoSmithKline, and Amgen. Dr Kwan has received research grants from the National Health and Medical Research Council of Australia, the Australian Research Council, the US National Institutes of Health, Hong Kong Research Grants Council, Innovation and Technology Fund, Health and Health Services Research Fund, and Health and Medical Research Fund. He and/or his institution also received speaker or consultancy fees and/or research grants from Eisai, GlaxoSmithKline, Johnson & Johnson, Pfizer, and UCB Pharma. No other disclosures are reported.

Figures

Figure 1.
Figure 1.. Antiepileptic Drug Regimens Over the Study Period
A, All antiepileptic drug (AED) regimens. B, All AEDs prescribed as a first monotherapy. The colored areas represent each antiepileptic drug as a proportion of all the antiepileptic drugs given to the full study cohort (n = 1795) in the corresponding years. The category “Other antiepileptic drugs” includes vigabatrin, felbamate, tiagabine, rufinamide, eslicarbazepine, retigabine, perampanel, and unnamed trial drugs. The yellow dashed lines divide the established AEDs from the new AEDs.
Figure 2.
Figure 2.. Cumulative Probability of 1-Year Seizure Freedom by Treatment Duration and Number of Antiepileptic Drugs Regimens Tried
A, Data for all patients; B, Patients with generalized epilepsy; C, Patients with focal epilepsy. In A, probabilities of seizure freedom differ significantly between first and second regimens, between second and third regimens, and between third and fourth regimens. In both B and C, patients who tried more than 3 antiepileptic drugs were grouped together in the subanalyses owing to small sample sizes; probabilities varied significantly between both first and second regimens and second and third regimens.
Figure 3.
Figure 3.. Increases in Probability of 1-Year Seizure Freedom for Each Additional Antiepileptic Drug Regimen Tried
The percentage of patients achieving seizure freedom via the first, second, third, fourth, fifth, sixth, and seventh AED regimens were 50.5%, 11.6%, 0.99%, 1.34%, 0.28%, and 0.94%, respectively. Please see Table 2 for numbers of patients achieving seizure freedom and total patients in each subgroup.
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Comment in

References

    1. Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia. 2010;51(5):883-890. - PMC - PubMed
    1. Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med. 2011;365(10):919-926. - PubMed
    1. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314-319. - PubMed
    1. Bialer M, White HS. Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010;9(1):68-82. - PubMed
    1. Brodie MJ, Kwan P. Newer drugs for focal epilepsy in adults. BMJ. 2012;344:e345. - PubMed

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