Associations of Baseline Seizure Frequency with Seizure Frequency Reduction in Blinded Clinical Trials of Antiseizure Medications
Abstract number :
1.508
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2025
Submission ID :
1262
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Advith Reddy, BS – University of Pittsburgh Neurology
Neo Kok, BS – University of Pittsburgh Neurology
Katie McFarlane, MS – University of Pittsburgh Neurology
Lavanya Biju, BS – University of Pittsburgh Neurology
Jacqueline French, MD – Department of Neurology and Comprehensive Epilepsy Center, New York University Grossman School of Medicine, NYU Langone Health
Wesley Kerr, MD, PhD – University of Pittsburgh Neurology
Rationale: Inclusion and exclusion criteria of clinical trials for seizures aim to select representative participants with a high enough seizure frequency to evaluate the efficacy of treatment in a relatively short double-blind period. A recent challenge has arisen where fewer participants had sufficiently high seizure frequency for inclusion and the rate of placebo response has been progressively increasing. To evaluate those patterns and inform the selection of seizure frequency-based inclusion criteria, we evaluated the association between baseline seizure frequency and the reduction of seizure frequency in the double-blind period.
Methods: Using data from 11 double-blind placebo-controlled trials of antiseizure medications for either focal- (7) or generalized-onset (4) epilepsy, we evaluated the association of baseline seizure frequency with 50% responder rate (50RR) and percent reduction of seizure frequency (PRSF) in maintenance. We grouped trials based on the presence or absence of significant association (p<0.05) in placebo or active treatment using mixed effects generalized linear models. We also evaluated whether the Time to Prerandomization monthly Seizure Count (T-PSC) design would impact these associations.
Results: In 55% (6/11) of trials had no significant association between baseline seizure frequency and 50RR and PRSF, but a meta-analysis across these trials identified a significant increase in 50RR and PRSF both in placebo and active treatment (NCT00136019, NCT00220415, NCT00464269, NCT00504881, NCT00236704, NCT00104416). In 18% (2/11) of trials, there was a significant association where lower baseline seizure frequency had higher 50RR and PRSF in both placebo and active treatment (NCT00043901; NCT01261325). In one trial (1/11), a ceiling effect was observed where the shift was observed in placebo only which resulted in reduced difference between placebo and active treatment (50RR 77.8%, NCT00160550). In the remaining 18% (2/11) trials, 50RR and PRSF was higher in participants with lower baseline seizure frequency with active treatment only and not placebo, indicating potential increased efficacy for lower baseline seizure frequency (NCT00490035; NCT00113165). These associations were not modified when the T-PSC design was used.
Conclusions: The association of the magnitude of change in seizure frequency with baseline seizure frequency was inconsistent across trials. In 82% (9/11) trials, there was individual or meta-analytic evidence of increases in both placebo and active treatment response in lower seizure frequencies. That shift may have reduced the power of one trial. However, in two trials, that pattern in active treatment but not placebo indicated potentially higher efficacy in lower seizure frequencies.
Funding: US National Institute for Neurological Disorders and Stroke (NIH K23NS135134, R25NS089450, NIH U24NS107158), the American Epilepsy Society, the Epilepsy Foundation, the American Academy of Neurology, the American Brain Foundation, and the UPMC Competitive Medical Research Grant.
Anti-seizure Medications