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. 2022 Dec;7(4):598-607.
doi: 10.1002/epi4.12632. Epub 2022 Aug 8.

Differences between men and women in response to antiseizure medication use and the likelihood of developing treatment resistant epilepsy

M Soledad Cepeda  1 , Rachel E Teneralli  2 , David M Kern  1 , Gerald Novak  3
Affiliations

Differences between men and women in response to antiseizure medication use and the likelihood of developing treatment resistant epilepsy

M Soledad Cepeda et al. Epilepsia Open. 2022 Dec.

Abstract

Objective: The prevalence of epilepsy is slightly higher in women than in men and sensitivity to seizure stimuli differs between sexes. Some evidence suggests sex differences in response to antiseizure medications exist mainly due to inconsistent pharmacokinetic differences; however, there is a lack of real-world evidence examining differences in response to antiseizure medications between men and women.

Methods: This was a retrospective population-based cohort study in five large US healthcare databases. The population included adult patients with epilepsy, newly exposed to levetiracetam, and naive to antiseizure medication. The first exposure to levetiracetam was the index date. The requirement that all patients received the same medication was done to avoid potential confounding due to differences in index treatment. The outcome was the development of treatment resistant epilepsy (TRE), defined as having at least three distinct antiseizure medications in 1 year. The proportion of patients who developed TRE within 1 year following the index date was calculated. To compare the risk of developing TRE between sexes, relative risks (RR) and 95% confidence intervals (CI) were calculated, and estimates were pooled using meta-analytic techniques stratified by gender and age.

Results: A total of 147 334 subjects were included in the databases, 50.8% were women, and 4.27% developed TRE. The comorbid profile differed greatly between men and women; however, the types of epilepsy syndromes observed during baseline were similar between the two groups. Across all databases, women were more likely to develop TRE than men (pooled RR 1.27, 95% CI 1.17-1.38). Results remained similar when stratified by age.

Significance: This study assessed sex differences in response to antiseizure medications using the development of TRE as a proxy for effectiveness. Women newly exposed to levetiracetam were 27% more likely to develop TRE than men, independent of age.

Keywords: epilepsy; real-world evidence; sex differences; treatment resistance.

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Conflict of interest statement

DMK, RET, and GN are employees of Janssen and have stock interests in Johnson & Johnson. MSC was an employee of Janssen R&D when the study was conducted and the manuscript was drafted. 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.

Figures

FIGURE 1
FIGURE 1
Risk of developing treatment resistant epilepsy (TRE) in women compared to men in each of the five databases. CCAE, IBM MarketScan® commercial database; CI, confidence interval; IQVIA, the IQVIA® adjudicated health plan claims data; MDCD, IBM® MarketScan® multi‐state Medicaid database; MDCR, IBM® MarketScan® Medicare supplemental database; OPTUM, Optum® De‐identified Clinformatics® data Mart database; RR, risk ratio; TRE, treatment resistant epilepsy.
FIGURE 2
FIGURE 2
Pooled risk of developing treatment resistant epilepsy (TRE) in women compared to men by age categories. RR, risk ratio; TRE, treatment resistant epilepsy.
See this image and copyright information in PMC

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References

    1. Collaborators GUND , Feigin VL, Vos T, Alahdab F, Amit AML, Barnighausen TW, et al. Burden of neurological disorders across the US from 1990‐2017: a global burden of disease study. JAMA Neurol. 2021;78(2):165–76. - PMC - PubMed
    1. Cepeda MS, Reps J, Kern DM, Stang P. Medical conditions predictive of self‐reported poor health: retrospective cohort study. JMIR Public Health Surveill. 2020;6(1):e13018. - PMC - PubMed
    1. Lekoubou A, Bishu KG, Ovbiagele B. Costs and cost‐drivers of a diagnosis of depression among adults with epilepsy in the United States. Epilepsy Behav. 2019;98:96–100. - PubMed
    1. Tian N, Zack M, Wheaton AG, Greenlund KJ, Croft JB. Epilepsy and chronic obstructive pulmonary disease among U.S. adults: National Health Interview Survey 2013, 2015, and 2017. Epilepsy Behav. 2020;110:107175. - PMC - PubMed
    1. Medina AE, Manhaes AC, Schmidt SL. Sex differences in sensitivity to seizures elicited by pentylenetetrazol in mice. Pharmacol Biochem Behav. 2001;68(3):591–6. - PubMed