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OBJECTIVE: This study aimed to explore the impact of co-antiseizure medication (co-ASM) optimization on the effectiveness and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy in a real-world setting. METHODS: This unicentric, retrospective, observational study included adults with focal-onset seizures who had received ≥2 previous ASMs. The main effectiveness endpoints included responder rates and seizure frequency reduction at 3, 6, and 12-month visits. The number of co-ASMs and defined daily dose (DDD) were analyzed at every visit. Safety endpoints included adverse drug reactions (ADRs). RESULTS: Thirty-four patients with a median epilepsy duration of 22 years and a median of 15.5 seizures/month were analyzed. The median number of prior ASMs was 12, and the mean number of co-ASMs was 2.9 (SD 1). There was a reduction in seizure frequency/month from baseline to the last visit (p < 0.0001). Between baseline and the end of the study, the mean number of co-ASMs in the per-protocol (PP) population was reduced from 2.9 to 1.6 (p < 0.0001), and DDD was reduced from 3.6 to 1.4 (p < 0.0001). Sodium channel blockers (carbamazepine and lacosamide) and GABAergic drugs (clobazam) were the agents with the most significant reductions in DDD after 12 months. The percentage of patients in the PP population with ≥3 co-ASMs was reduced from 61.8% at baseline to 14.3% at 12 months; 1 patient was receiving CNB as monotherapy at the last visit. At the last visit, 85.7% of the PP population were ≥50% responders, and 33.3% were seizure-free. The percentage of patients with ADRs in the PP population was 71.9% at 3 months and 52.3% at 12 months. SIGNIFICANCE: Following rational polytherapy, optimization of co-ASM management during CNB treatment allowed high seizure freedom rates despite meaningful reductions in co-medication, while also achieving both good tolerability and patient satisfaction scores in a highly drug-resistant population. PLAIN LANGUAGE SUMMARY: Many patients with epilepsy still have seizures, even after being treated with several different epilepsy drugs. In this study of 34 patients from a Spanish clinic, we show that the epilepsy drug cenobamate can reduce the number of seizures in these patients, even after many other epilepsy drugs have failed. We also show that patients treated with cenobamate can reduce the dose or even stop taking certain other epilepsy drugs. This allows them to simplify their treatment and reduce adverse effects while still keeping control of their epilepsy.
RESUMO
(1) Background: The impact of the health crisis caused by coronavirus disease 2019 (COVID-19) has provoked collateral effects in the attention to pathologies with time-dependent treatments such as strokes. We compare the healthcare activity of two stroke units in the same periods of 2019 and 2020, with an emphasis on what happened during the state of alarm (SA). (2) Materials and methods. Hospitals in the region implemented contingency plans to contain the pandemic; in this planning, the stroke units were not limited in their operational capacity. The SA was declared on 15 March and remained in place for 10 weeks. For the analysis, the data were grouped by consecutive calendar weeks. (3) Results. When the SA was declared the number of calls to the emergency telephone went from 1225 to 3908 calls per week (318% increase). However, the activation of the stroke code went from 6.6 to 5.0 (p = 0.04) and the activity in both stroke units decreased. The largest drop in hospitalizations was for transient ischemic attacks (TIAs) with 35.7% less, 28 vs. 18, (p = 0.05). Reperfusion therapies fell by 37.5%; Poisson regression model 0.64; (95% confidence interval (CI), 0.43-0.95). The overall activity of the telestroke suffered a reduction of 28.9%. We also observed an increase in hospital mortality. (4) Conclusion. The excessive duration of the pandemic precludes any hope of resolving this public health crisis in the short or medium term. Further studies should be conducted to better understand the multifactorial nature of this dramatic decline in stroke admissions and its negative impact.