Heterogeneity of Effects from Antiseizure Medication Withdrawal on Seizure Risk Increase Among Patients with Well-controlled Epilepsy: A Pooled Analysis
Abstract number :
1.288
Submission category :
7. Anti-seizure Medications / 7C. Cohort Studies
Year :
2023
Submission ID :
8
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Samuel Terman, MD MS – University of Michigan
Geertruida Slinger, MD – University Medical Center Utrecht; Adriana Koek, MD – University of Michigan; Jeremy Skvarce, BS – University of Michigan; Mellanie Springer, MD MS – University of Michigan; Julie Ziobro, MD PhD – University of Michigan; James Burke, MD MS – Ohio State University; Willem Otte, PhD – University Medical Center Utrecht; Roland Thijs, MD PhD – Stichting Epilepsie Instellingen Nederland; Morten Lossius, MD – University of Oslo; Anthony Marson, MD – University of Liverpool; Laura Bonnett, PhD – University of Liverpool; Kees Braun, MD PhD – University Medical Center Utrecht
Rationale: Guidelines suggest considering antiseizure medication (ASM) discontinuation in seizure-free patients with epilepsy. Past work has explored average seizure risk increases but not how discontinuation effects vary between patients. We explored 1. What factors modify the influence of discontinuation on seizure risk, and 2. The range of seizure risk increases due to discontinuation across different “baseline” (post-discontinuation) risks.
Methods: We pooled datasets including seizure-free patients who did and did not discontinue ASMs: two randomized controlled trials (RCTs) plus a three-center retrospective cohort. We conducted time-to-first-seizure analyses using discrete time logistic regressions. First, we evaluated what individual patient factors modified the relative effect of ASM discontinuation on seizure risk via interaction terms. Then, we assessed the distribution of risk increase and number needed to harm (NNH; number discontinuing ASMs to cause relapse in one) at different baseline risks.
Results: We included 1,626 patients (Medical Research Council 1991 RCT: 1,013; Lossius et al 2008 RCT: 149; Terman et al 2023 retrospective cohort: 464) of whom 678 (42%) planned to discontinue all ASMs. The mean predicted two year seizure risk was 43% (95% confidence interval [CI] 39%-46%) for discontinuation versus 21% (95% CI 19%-24%) for continuation. The mean two year absolute seizure risk increase was 21% (95% CI 17%-25%). No individual interaction term was significant after correcting for multiple comparisons. The median (interquartile range [IQR]) risk increase across levels of baseline risk was 19% (IQR 14%-24%). This translates to a median NNH of 5 (IQR 4-7; range 3-14).
Conclusions: Overall baseline risk determines absolute risk increase due to discontinuation far more than any single patient characteristic. We described the ranges of seizure risk increase that patients may expect due to discontinuation at different levels of baseline risk. Future work will use these results to develop a two-armed individualized seizure risk calculator and contextualize how large seizure risk reductions should be to outweigh treatment burden.
Funding: Susan S Spencer Clinical Research Training Scholarship and the Michigan Institute for Clinical and Health Research J Award UL1TR002240 (Dr Terman).
Anti-seizure Medications