Clinical Practice and Patient Burden Associated With Antiseizure Medication Titration: A Thematic Analysis

• This patient and physician research revealed titration is rarely part of the dialogue among physicians, despite titration’s effect on clinical management complexity and increased strain on healthcare resources • These findings underscore the substantial and potentially overlooked burden associated with ASM titration on patients and physicians, highlighting the need for improved communication between patients and physicians, as well as the need for ASMs that require simplified or no titration • Increasing awareness of the burden of titration within the wider epilepsy community may improve shared decision-making through recognition of titration-related factors that may negatively impact the patient experience with ASMs Poster: P0010 | 16th European Epilepsy Congress | September 5-9, 2026 | Athens, Greece INTRODUCTION • Epileptic seizures are classified by onset and clinical presentation, including focal, generalized, unknown (whether focal or generalized), and unclassified.1 Of these, focal seizures (FS) account for approximately 60% of the ~3 million adults with epilepsy in the US2,3 • Most antiseizure medications (ASMs) recommend slow titration to improve tolerability, potentially delaying therapeutic dosing and optimal seizure control.4 The titration of ASMs for FS can take months, and patients may struggle with complex titration schedules5 • While ASMs include US Food and Drug Administration (FDA)-recommended titration instructions, the titration process is often individualized on various factors including patient characteristics and ASM-specific factors4,5 • Although the challenges of ASM titration have been described, there remains a gap in understanding how patients with FS and healthcare providers (HCPs) experience this process in real-world practice Clinical Practice and Patient Burden Associated With Antiseizure Medication Titration: A Thematic Analysis John M. Stern, 1 Danielle A. Becker,2 Steve S. Chung, 3 Micheál Macken, 4 David King-Stephens, 5 Andrew J. Zillgitt, 6 Mohamad Z. Koubeissi, 7 Brad Padilla,8 Alvin Ong9 1UCLA School of Medicine, Los Angeles, CA, USA; 2The Ohio State University Wexner Medical Center, Columbus, OH, USA; 3University of Arizona Banner–University Medical Center, Phoenix, AZ, USA; 4Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5University of California Irvine, Irvine, CA, USA; 6Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA; 7George Washington University, Washington, DC, USA; 8Stratevi, Santa Monica, CA, USA; 9Xenon Pharmaceuticals Inc., Vancouver, BC, Canada CONCLUSIONS METHODS Participants: Patients With FS • A cross-sectional, web-based survey was conducted in January 2025 among patients with a physician-confirmed diagnosis of FS. The study was approved by an institutional review board (IRB) (WCG IRB, Cary, NC) • Participants completed a screening survey and were eligible if they had tried and stopped ≥1 ASM within the past year and either (a) had both an office visit and used an ASM requiring titration and/or dose escalation/modificationa within the past year, or (b) were currently using or initiating an ASM requiring titration and/or dose escalation/modification and had no history of psychogenic nonepileptic seizures, Dravet syndrome, Lennox-Gastaut syndrome, or other developmental and epileptic encephalopathies • Data collected included demographics, clinical history, and epilepsy-specific quality-of-life measures. The survey also assessed factors influencing ASM selection, adherence, side effects, dose modifications, healthcare resource utilization (HCRU), and challenges and emotions experienced during titration • Outcomes were summarized using descriptive statistics, including means and standard deviations (SDs) for continuous variables and frequency counts and percentages for categorical variables OBJECTIVE • To assess both patient and HCP perspectives on the practical realities of ASM titration, focusing on identifying key unmet needs and defining the burden on both patients with FS and HCPs who directly treat these patients RESULTS Participants: Patients With FS • Demographic characteristics of the surveyed patients with FS (N=48) are summarized in Table 1 Table 1. Patient Characteristics Patient Characteristics (N=48) Age (N=45)a Mean (SD) 35 (13) Median (range) 32 (19-70) Sex, n (%) Female 21 (44) Male 27 (56) Ethnicity, n (%)b White 20 (42) Hispanic or Latino 13 (27) Black or African American 9 (19) Asian/Pacific Islander 5 (10) Native American or American Indian 1 (2) Age at diagnosis of epilepsy (N=45)a Mean (SD) 24 (16) Median (range) 22 (0-65) aData regarding age and age at diagnosis of epilepsy are missing for n=3 patients. bRespondents were able to select all response options that applied; therefore, the responses are not mutually exclusive.

SD, standard deviation.

Participants: Physician Experts • Characteristics of the participating physicians (N=7) are summarized in Table 2; all were epileptologists treating a mean of 95 patients with FS per month Table 2. Physician Expert Characteristics Physician Expert Characteristics (N=7) Primary specialty, n (%) Epileptologist 7 (100) Setting of practice, n (%) Academic medical hospital 7 (100) Years in practice since completing their education Mean (SD) 20 (7) Median (range) 25 (10-26) Patients with FS treated per month Mean (SD) 95 (21) Median (range) 100 (70-120) FS, focal seizures; SD, standard deviation.

Thematic Analysis • The main theme and emerging subthemes from the roundtable are shown in Figure 1 References: 1. Beniczky S, et al. Epilepsia. 2025;66(6):1804-1823. 2. Gupta S, et al. Epilepsia Open. 2017;2(2):199-213. 3. Zack MM, et al. MMWR Morb Mortal Wkly Rep. 2017;66(31):821-825.

4. Seiden LG, et al. Epilepsy Behav. 2022;128:108517. 5. Williams B, et al. Epilepsy Behav. 2021;117:107840. 6. Caffrey AR, et al. Ther Adv Drug Saf. 2021;11:2042098620958910.

Greater Complexity of Clinical Management • Physicians reported that cross-titration, the process of decreasing the dose of 1 drug while simultaneously increasing the dose of another drug when switching between medications or initiating combination therapy, is largely guided by expert consensus and associated with unpredictable outcomes • During cross-titration, physicians shared that they balance multiple, often competing considerations, including DDIs that add complexity, particularly when complications arise (Figure 2) • Physicians also reported that complex dosing schedules (eg, multiple daily administrations and variable day-to-day doses) can negatively impact adherence • Patients with FS reported concerns they experienced during the titration of their ASM, including worry about having FS during the titration process (56%) and not having a clear understanding of the titration process (35%) (Figure 3) ACKNOWLEDGMENTS: The authors would like to thank Diane Ito, Josephine Li-McLeod, and Ava Maurillo from Stratevi for their contributions to data analysis, medical writing, and editorial support of this poster. Additional editorial support was provided by Heidi Reinholdt, MS, MA, CMPP , of Helios Global Group and was funded by Xenon Pharmaceuticals Inc. (Vancouver, BC, Canada). Xenon Pharmaceuticals Inc. reviewed and provided feedback on the poster. The authors had full editorial control of the poster and provided their final approval of all content.

DISCLOSURES: John M. Stern has been a consultant and speaker for Ceribell, Jazz Pharmaceuticals, LivaNova, Neurelis, SK Life Science, UCB, and Xenon Pharmaceuticals Inc. (advisory board). Danielle A.

Becker has been a consultant and speaker for Jazz Pharmaceuticals, LivaNova, Neurelis, NeuroPace, SK Life Science, and Xenon Pharmaceuticals Inc. (advisory board). Steve S. Chung has been a speaker for Neurelis, and a consultant and speaker for Jazz Pharmaceuticals, SK Life Science, UCB, and Xenon Pharmaceuticals Inc. (advisory board). Micheál Macken has been a consultant and speaker for Jazz Pharmaceuticals, SK Life Science, UCB, and Xenon Pharmaceuticals Inc. (advisory board). David King-Stephens has been a speaker for Neurelis, NeuroPace, SK Life Science, UCB, and Xenon Pharmaceuticals Inc. (advisory board). Andrew J. Zillgitt has been a speaker for Jazz Pharmaceuticals and SK Life Science, and a consultant and speaker for Catalyst, UCB, and Xenon Pharmaceuticals Inc. (advisory board).

Mohamad Z. Koubeissi has been a speaker for SK Life Science and Xenon Pharmaceuticals Inc. (advisory board). Brad Padilla is an employee of Stratevi, a research consulting company, receiving funding from Xenon Pharmaceuticals Inc. to conduct this study. Alvin Ong is an employee of and owns stock or stock options in Xenon Pharmaceuticals Inc.

FUNDING: This study is funded by Xenon Pharmaceuticals Inc.

These data were previously presented at the American Epilepsy Society Annual Meeting, December 5-9, 2025, Atlanta, GA, USA.

Participants: Physician Experts • A moderated physician roundtable was conducted in April 2025 among US board- certified physicians (MD/DO) who treat patients with FS and met the following eligibility criteria: manage ≥25 patients with FS per month (with ≥50% initiating or undergoing ASM titration or dose escalation/modificationa), currently manage ≥5 patients meeting the patient-survey inclusion criteria, have current or prior experience prescribing titration-requiring ASMs, and are willing and able to complete a 30-minute interview on ASM switching and outcomes • Prior to the roundtable discussion, each physician participated in a 30-minute, semistructured interview about their practices and perspectives across the titration process, including initial dosing strategies, monitoring techniques, adherence to prescribing guidelines, and challenges with drug-drug interactions (DDIs) • Data from the patient survey and physician interviews informed the roundtable agenda and discussion topics • The roundtable discussion was transcribed and analyzed using thematic analysis; analysts independently coded the transcript, reconciled discrepancies by consensus, and organized salient themes Figure 1. Main Theme and Subthemes Emerging From the Roundtable Greater complexity of clinical management Increased strain on healthcare resources Underrecognized burden of titration to both patients and HCPs ASM titration burden ASM, antiseizure medication; HCP , healthcare provider.

Figure 2. Cross-Titration Considerations Cross-titration process Tolerability Seizure control DDI (PK/PD) Safety Medication burden Patient adherence DDI, drug-drug interaction; PD, pharmacodynamics; PK, pharmacokinetics.

Figure 3. Patient-Reported Concerns Experienced During Titration (N=48) 6% 15% 17% 21% 35% 56% 0% 20% 40% 60% Other Titration felt too long I experienced negative emotions during the titration process I did not have any of these concerns I was uncomfortable talking to my doctor about the titration process I did not have a clear understanding of the titration process I was worried about having FS during the titration process Percentage of patientsa aRespondents were able to select all response options that applied; therefore, the responses are not mutually exclusive.

Question: During the titration (the time when your doctor gradually adjusts your medication dose to find the right amount that works best for you) of [index ASM], did you have any of the following concerns? Please select all that apply.

ASM, antiseizure medication; FS, focal seizures.

• Patients with FS also reported that the time and number of clinic visits/phone calls needed to reach the target dose (60%) and keeping up with multiple ASM dose adjustments (44%) were challenges they encountered during ASM titration (Figure 4) Figure 4. Patient-Reported Challenges Encountered During Titration (N=48) 13% 40% 44% 60% 0% 20% 40% 60% I did not find anything to be challenging Difficulty in understanding & learning about the titration process Keeping up with all of the dose adjustments of my ASM Time required & number of clinic visits/ phone calls needed to reach the target dose Percentage of patientsa aRespondents were able to select all response options that applied; therefore, the responses are not mutually exclusive.

Question: During the titration (the time when your doctor gradually adjusts your medication dose to find the right amount that works best for you) of [index ASM], what challenges did you face, if any? Please select all that apply.

ASM, antiseizure medication.

Increased Strain on Healthcare Resources • Physicians reported that ASM titration is associated with increased HCRU, spanning both quantifiable events (eg, emergency department visits) and less easily measured burden (eg, communication workload) • During titration, physicians identified the following increases in HCRU (Figure 5): – Increased reliance on clinic staff to triage calls and provide patient support – Higher volume of patient communication (emails and portal messages) – More frequent follow-up clinic visits to monitor patients during titration – Additional time spent developing/updating titration schedules and educational materials – Greater coordination with pharmacists to convey titration instructions and confirm prescriptions Figure 5. Physician Expert Reports of Increased HCRU Related to Titration “There's a lot of micromanagement that has to be done. And the process is going to take at least I think 6 months to a year to try to get to the target. It's very slow and labor-intensive for sure.” “I have a nurse practitioner that helps [field phone calls]. If I didn’t have her, it would make my life super difficult. There is a patient who required weekly phone calls…”

Reliance on staff “When I communicate with patients between visits, I don't bill for it, so it doesn't show up in the [economics], but it consumes my time, which I think does have value.”

Communication workload “I write out the instructions to the pharmacy. I write out the instructions for the patient.

I put it in their patient instructions… I make sure that they get [their ASM], and that the pharmacy knows it's there.”

Frequent follow-up visits “I type out the entire titration… It is exhausting, it takes up resources… I spend probably an extra 10-15 minutes going over [instructions] to make sure they understand it… It is a lot of education and teaching…”

Titration education Coordination with pharmacists ASM, antiseizure medication; HCRU, healthcare resource utilization.

Underrecognized Burden of Titration • Physicians previously viewed titration as routine and may not have fully appreciated the challenges experienced by patients and nonspecialist HCPs. All (100%) agreed that the burden of titration is greater than what is generally recognized (Figure 6) • Patient-reported data were consistent with physician observations that titration burden may be underrecognized during titration; patients worried about breakthrough seizures (Figure 3) and reported difficulty keeping up with ASM dose adjustments and understanding the titration steps (Figure 4) Figure 6. Physician Expert Insights on the Burden of Titration “What’s simple, sometimes, is because we [the physicians] have done it a lot.

So, it doesn’t feel complicated… but then when you look at it, you realize that is not [the case].” “We are adding [ASMs] to get better efficacy because of this concept of polytherapy and rational polypharmacy… even if that medication had some efficacy, you have got to lower [its dose] because of [its pharmacodynamic and pharmacokinetic interactions]. You have to take that risk, which comes back to the stress of all of this.” “What is a straightforward titration to me is straightforward because I have done it over and over again, and to the patient, they have never done it before… to the patient, everything is [unfamiliar].”

ASM, antiseizure medication. aDose escalation/modification is considered different from titration, which is FDA-recommended to reach a therapeutic dose.

Dose escalation/modification could be 1) increasing the dose after reaching a therapeutic dose, 2) reducing the dose over time, or 3) cross-titration, which indicates decreasing the dose of 1 drug while simultaneously increasing the dose of another drug.8