Abstracts

Rationale: Although nearly 20 antiseizure medications (ASMs) have been approved in the United States (US) and Europe in the past three decades, none have been approved for neonates. Hence, off-label use of new ASMs in neonates is common. Lacosamide (LCM) could be a useful medication for the management of seizures in neonates, but there is no evidence available on the safety or effectiveness of LCM use in neonates. We conducted a retrospective cohort study to evaluate the real-world safety and effectiveness of LCM.

Methods: A multicenter (7 pediatric hospitals part of PEDSnet in US) retrospective cohort study was conducted using data from electronic health records from 01Jan2009 to 29Feb2020. Patients aged < 30 days born at gestational age of at least 35 weeks and treated with at least one dose of LCM were followed for up to 30 days from index date (first LCM dose). Newly diagnosed health conditions were extracted from patient charts by trained medical personnel. Effectiveness of LCM was assessed by a neonatal neurologist based on available clinical data and electroencephalogram (EEG) reports for up to 3 days following initiation of LCM treatment.

Results: Forty-seven neonates met the study selection criteria. The mean age (standard deviation [SD]) at index date and mean birthweight (SD) were 13.9 (9.4) days and 3.0 (0.6) kg, respectively. Almost all neonates (n=46; 97.9%) received a first dose of LCM in an intensive care unit and were treated with several other ASMs before index date, including phenobarbital (n=37; 78.7%), fosphenytoin (n=29; 61.7%), and levetiracetam (n=27; 57.4%). The median number of days on LCM was 10 (range 1–30) days. Nine patients (19.1%) received LCM through the end of the follow-up period. Nineteen patients (40.4%) were prescribed LCM at transfer or discharge. During the median safety follow-up of 12 (interquartile range 7–28) days, the crude incidence rate per 1000 person days of health conditions by diagnostic categories were 10.49 (95% confidence interval [CI]: 4.22–21.62) for cardiac conditions, 4.38 (95% CI: 0.90–12.80) for skin and subcutaneous tissue disorders, 2.81 (95% CI: 0.34–10.16) for blood or lymphatic system disorders and for nervous system disorders, each. Nine deaths (19.1%) were observed in the cohort. Physicians caring for these patients did not attribute any health conditions to LCM. EEG data were available for 34 patients and confirmed the presence of electrographic seizures in 31 patients, including 15 neonates (44.1%) with electrographic status epilepticus on the index date. Effectiveness assessment based on EEG reports was possible in 18 patients. On day 1, nine out of 18 patients (50%) improved and three patients (16.7%) had an improvement in seizure burden of greater than 50%.

Conclusions: The results from this study indicate LCM is being used to treat neonates with seizures, is not associated with safety events attributable to LCM, and may be effective, with half of the patients showing improvement in seizures. Further controlled studies are required to confirm the safety and effectiveness of LCM for neonatal seizures.

Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-funded.