Abstracts

Rationale: Intravenous lacosamide (IV LCM) could be useful for seizure management in young children given its quick mode of administration and established safety profile in older children and adults. However, few studies have assessed the safety of IV LCM in children. At the time of the study, IV LCM was not approved for use in children in the United States. The extrapolated dose used in the pediatric population was calculated from the recommended dose in adults. Any LCM dose higher than the dose extrapolated from the recommended dose in adults was defined as the higher dose. The off-label use of higher doses in pediatric patients has not been studied yet. We evaluated the safety of initiating IV LCM at extrapolated dose vs higher dose in pediatric patients with drug-resistant seizures.

Methods: We conducted a retrospective cohort study using electronic health records data (01 Jan 2009–29 Feb 2020) from PEDSnet (7 large pediatric hospitals in the United States). Patients aged ≥ 1 month to < 17 years, treated with ≥ 1 IV LCM dose and not exposed to LCM for 3 months before the index date (first IV LCM dose) were included. Based on first IV LCM dose and patient age and weight, patients were classified into two groups: extrapolated dose cohort and higher dose cohort. Patients were followed until discharge or transfer from hospital for a maximum of 37 days. Newly diagnosed health conditions were extracted by trained medical personnel who were blinded to full study protocol. Incidence rate ratios (IRR) were adjusted for possible confounders by Poisson regression with inverse probability treatment weights.

Results: Among 686 children, 68.7% vs 31.3% were in the extrapolated and higher dose cohorts, respectively (mean age: 6.9 vs 7.6 years; male: 56.1% vs 55.3%). Over half were treated in an intensive care unit. One third of patients (36.7% vs 32.6%) were hospitalized in the 3 months before the index date. The median number of antiseizure medications before index date was 5 in the extrapolated dose cohort vs 4 in the higher dose cohort. During the median follow-up of 7 days, crude incidence rates per 1000 person-days of overall health conditions were 64.44 (95% confidence interval [CI]: 55.88–73.95) in the extrapolated vs 50.00 (95% CI: 39.82–61.98) in the higher dose cohort. Crude incidence rates per 1000 person-days of overall health conditions that physicians attributed to LCM in medical records were 0.98 (95% CI: 0.36–2.12) in the extrapolated vs 1.37 (95% CI: 0.37–3.51) in the higher dose cohort. In multivariate analyses, a two-fold increase in the risk of rash in the higher dose cohort vs the extrapolated dose cohort (adjusted IRR 2.11; 95% CI: 1.02–4.38) was observed. Forty-seven deaths were reported; none were attributed to LCM. Crude mortality rates per 1000 person-days were 4.77 (95% CI: 3.22–6.80) in the extrapolated and 5.67 (95% CI: 3.30–9.06) in the higher dose cohorts. After adjusting for confounding variables, no statistically significant IRRs were observed in the higher dose cohort vs the extrapolated dose cohort (adjusted IRR 1.18; 95% CI: 0.57–2.42).

Conclusions: The findings of this large contemporary observational study are consistent with previously established LCM safety profile.

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