Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2021 May;62(5):1119-1129.
doi: 10.1111/epi.16880. Epub 2021 Mar 18.

First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid

Pim B van der Meer  1 , Linda Dirven  1   2 , Marta Fiocco  3   4 , Maaike J Vos  2 , Mathilde C M Kouwenhoven  5 , Martin J van den Bent  6 , Martin J B Taphoorn  1   2 , Johan A F Koekkoek  1   2
Affiliations
Observational Study

First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid

Pim B van der Meer et al. Epilepsia. 2021 May.

Abstract

Objective: This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.

Methods: In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow-up was 36 months.

Results: In total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%-38%] vs 50% [95% CI 45%-55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%-19%] vs 28% [95% CI 23%-32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%-18%] vs 15% [95% CI 11%-18%]; P = .636).

Significance: Our results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first-line AED treatment in patients with glioma.

Keywords: antiepileptic drug; glioma; levetiracetam; seizures; valproic acid.

PubMed Disclaimer

Conflict of interest statement

None of the authors declare a conflict of interest. We confirm that we have read the Journal's guidelines for ethical publication and affirm that this manuscript is consistent with these guidelines.

Figures

FIGURE 1
FIGURE 1
Time to treatment failure for any reason, from antiepileptic drug treatment initiation, in 858 matched patients: levetiracetam vs valproic acid. CI, confidence interval; CIF, cumulative incidence function; LEV, levetiracetam; no., number of patients; VPA, valproic acid
FIGURE 2
FIGURE 2
Time to recurrent seizure, from antiepileptic drug treatment initiation, in 858 matched patients: levetiracetam vs valproic acid. 1 Patients who experienced treatment failure (due to adverse effects, withdrawal due to remission of seizures, or other reasons) before experiencing their recurrent seizure can no longer experience a recurrent seizure on their first‐line monotherapy levetiracetam or valproic acid, and therefore, treatment failure was handled as a competing risk. CI, confidence interval; CIF, cumulative incidence function; LEV, levetiracetam; no., number of patients; VPA, valproic acid
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella‐Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20. - PubMed
    1. Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014;15:e395–403. - PubMed
    1. Samudra N, Zacharias T, Plitt A, Lega B, Pan E. Seizures in glioma patients: An overview of incidence, etiology, and therapies. J Neurol Sci. 2019;404:80–5. - PubMed
    1. Phan K, Ng W, Lu VM, McDonald KL, Fairhall J, Reddy R, et al. Association between IDH1 and IDH2 mutations and preoperative seizures in patients with low‐grade versus high‐grade glioma: a systematic review and meta‐analysis. World Neurosurg. 2018;111:e539–e545. - PubMed
    1. Maschio M, Aguglia U, Avanzini G, Banfi P, Buttinelli C, Capovilla G, et al. Management of epilepsy in brain tumors. Neurol Sci. 2019;40:2217–34. - PubMed

Publication types