| Contributors: |
Cerulli Irelli, E.; Cocchi, E.; Gesche, J.; Pena-Ceballos, J.; Caraballo, R. H.; Lattanzi, S.; Strigaro, G.; Morano, A.; Moloney, P. B.; Ferlazzo, E.; Pascarella, A.; Mazzeo, A.; D'Aniello, A.; Pizzanelli, C.; Milano, C.; Giuliano, L.; Viola, V.; Mostacci, B.; Fortunato, F.; Pulitano, P.; Burani, M.; Meletti, S.; Pignatta, P.; Perulli, M.; Battaglia, D.; Rosati, E.; Delanty, N.; Di Gennaro, G.; Gambardella, A.; Labate, A.; Operto, F. F.; Giallonardo, A. T.; Beier, C. P.; Di Bonaventura, C.; Baykan, B.; Fatuzzo, D.; Pastorelli, G.; Quarato, P.; Catania, C.; Casciato, S.; Martellino, C.; Atanasio, G.; Viglietta, E.; Cianci, V.; Bagnasco, I.; Cognolato, E.; Pronello, E.; Bisulli, F.; Pontrelli, G.; Boero, G.; Gilio, F.; Gragnani, F.; Marini, C.; Gasparini, S.; Pappalardo, I. |
| Description: |
Importance: Women with idiopathic generalized epilepsy (IGE) face challenges in treatment due to limited options that are both effective and safe. Objective: To evaluate the effectiveness and safety of substitution monotherapy vs add-on therapy as second-line options for women who might become pregnant with IGE after failure of first-line antiseizure medications (ASMs) other than valproic acid. Design, Setting, and Participants: Multicenter retrospective comparative effectiveness cohort study at 18 primary, secondary, and tertiary adult and children epilepsy centers across 4 countries, analyzing data from 1995 to 2023. Participants were women aged 10 to 50 years diagnosed with IGE who were prescribed a second line of ASM. Main Outcomes and Measures: Treatment failure (TF), defined as the replacement or addition of a second ASM due to ineffectiveness, was compared between patients receiving ASM add-on or substitution monotherapy using inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression. Exploratory analyses were also conducted to assess the effectiveness of individual ASMs and various ASM combinations. Results: This study included 249 women with a median (IQR) age of 18.0 (15.5-22.0) years. Among them, 146 (58.6%) received an add-on regimen, and 103 (41.4%) received substitution monotherapy. During follow-up, TF occurred in 48 patients (32.9%) receiving add-on therapy and 36 (35.0%) using substitution monotherapy, with no significant differences between groups (IPTW-adjusted hazard ratio [HR], 0.89; 95% CI, 0.53-1.51; P =.69). ASM discontinuation due to ineffectiveness or adverse effects occurred in 36 patients (24.7%) receiving add-on therapy and 29 (28.2%) receiving substitution monotherapy, showing no significant differences (IPTW-adjusted HR, 0.97; 95% CI, 0.57-1.65; P =.92). Rates of ASM discontinuation due to adverse effects only were low in both groups, occurring in 13 patients (9.0%) receiving add-on therapy and 9 (8.7%) receiving a substitution monotherapy. ... |