Long-Term Treatment Retention of Levetiracetam Monotherapy in Adults with Epilepsy: A 10-Year Retrospective Cohort Study Using Time-to-Treatment-Failure Analysis

Background: This study aimed to estimate treatment retention rates for levetiracetam monotherapy in patients with epilepsy and to characterize treatment failure in this population. Methods: A retrospective cohort study included 769 adult patients with epilepsy between 2015 and 2024 at a tertiary hospital in Saudi Arabia who initiated levetiracetam monotherapy. The date of levetiracetam initiation was designated as the index date, and patients were followed from that point until treatment failure or censoring. Treatment failure was defined as either discontinuation of levetiracetam because of adverse events or the addition of another antiseizure medication due to insufficient seizure control. Kaplan–Meier survival analysis was used to estimate the probability of remaining on levetiracetam monotherapy over the follow-up period. Differences in patient characteristics were assessed between the treatment-failure and success groups using Student’s t-test for continuous variables and either the chi-square test or Fisher’s exact test for categorical variables. Results: Of the 769 patients who initiated levetiracetam monotherapy, 143 (18.55%) experienced treatment failure during the 10-year follow-up period. The overall mean time to levetiracetam treatment failure was 93.58 months. The 25th percentile time to treatment failure was 95 months (95% CI: 60.167–103.133). The median time to treatment failure was not reached. Females comprised 50.3% of the cohort, with no significant difference in sex distribution between groups (p = 0.136). Patients in the treatment-failure group were younger (39.85 ± 16.88 vs. 45.76 ± 19.48, p = 0.0003), had higher estimated Creatinine clearance (CrCl) (132.19 ± 57.83 vs. 118.50 ± 61.15, p = 0.0150), and had predominantly generalized seizure onset (40.56% vs. 33.71%, p = 0.0182) compared with the treatment-success group. Conclusions: Levetiracetam monotherapy demonstrated sustained long-term treatment retention when used as first-line therapy in adults with epilepsy.