Poster · Epilepsy & Seizure Disorders
Real-World Dosing Patterns of Anti-Seizure Medications in Adult Epilepsy: A Retrospective Cohort Analysis of FDA Label Alignment and Influencing Factors
Emi Lin Luo, BS¹², Marissa Ludwig, BS¹², Lindsay Oshiro, BS¹², Kristal Xie, MS, MPH¹², Caroline Ulep²³, Carson Konop²⁴, Kammiee-Marie Ardo²⁵, Kyle Ishikawa, MS⁶, Darren Dugas, MD², Enrique Carrazana, MD², Barbara Pitts, PhD², Kore Liow, MD, FACP, FAAN²
- 1 John A. Burns School of Medicine, University of Hawaiʻi at Mānoa, Honolulu, HI ² Comprehensive Epilepsy Center, Hawaiʻi Pacific Neuroscience, Honolulu, HI ³ University of San Francisco, San Francisco, CA ⁴ Bishop Kelly High School, Boise, ID ⁵ Carnegie Mellon University, Pittsburgh, PA ⁶ Biostatistics Core Facility, Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaiʻi at Mānoa, Honolulu, HI
Introduction: Anti-seizure medications (ASMs) are the primary treatment for patients with epilepsy. Prior research has shown that clinical trial efficacy often diverges from real-world clinical effectiveness, with up to one-third of patients remaining refractory despite diverse therapeutic options. However, there is a lack of research evaluating how ASMs are prescribed in real-world clinical practice, their alignment with U.S. Food and Drug Administration (FDA) labeling guidelines, and the subsequent therapeutic response in ethnically diverse populations, particularly in Hawaiʻi.
Objective: To compare real-world maintenance doses of ASMs to FDA-labeled dose ranges, and evaluate the effects of ethnicity, demographics, seizure control status, and treatment regimen on dosing.
Results: Of the 206 patients, 159 were seizure-free and 47 had uncontrolled seizures. The median age in both groups was comparable (57 years [IQR 39,70] vs. 53 years [IQR 36,66]). There was a similar sex distribution between the two groups. Insurance status also did not differ significantly, with most patients in both groups covered by either private or public insurance. Native Hawaiian (36%) and White (27%) patients experienced the highest proportions of uncontrolled seizures among the racial groups evaluated. Patients with uncontrolled seizures were significantly more likely to be treated with polypharmacy than monotherapy (82% vs. 18%), whereas patients who were seizure-free were more likely to receive monotherapy than polypharmacy (58% vs. 42%) (p < 0.001). In terms of real-world dose deviations, the majority of patients within both groups remained below the FDA-recommended prescribed maximum daily dose. On average, prescribed maintenance doses reached 44% of the FDA-recommended maximum in the seizure-free group versus 40% in the uncontrolled group, though this trend was not statistically significant. The top 3 medications used in both groups were levetiracetam (n = 115), lamotrigine (n = 68), and lacosamide (n = 41). Medication-specific analyses revealed that topiramate was the only medication to reach a higher percentage of the FDA maximum in uncontrolled patients compared to seizure-free patients (38% vs. 25%, p = 0.047). Interestingly, cenobamate (81% vs. 50%, p = 0.095) and zonisamide (66% vs. 17%, p = 0.095) showed higher relative dosing limits within the seizure-free cohort. Lamotrigine and lacosamide remained completely uniform regardless of seizure control status.
Conclusion: Among patients treated with ASMs, demographic characteristics were generally similar between seizure-free and uncontrolled seizure groups. However, Native Hawaiian and White patients had the highest proportions of uncontrolled seizures, suggesting potential disparities that warrant further investigation. Overall, providers at this neurology facility in Hawaiʻi typically prescribe ASMs under the maximum FDA-recommended daily dose. Patients who have uncontrolled seizures were significantly more likely to be on a polypharmacy regimen than monotherapy, highlighting the clinical challenges associated with the management of drug-resistant epilepsy. These findings emphasize the importance of investigating more personalized therapeutic regimens for treatment-resistant epilepsy.