The effectiveness and safety of lacosamide in children with epilepsy in a clinical practice setting

Role of observational studies in supporting extrapolation of efficacy data from adults to children with epilepsy — A systematic review of the literature using lacosamide as an example

“…64,65 Tachyarrhythmia, as part of multi-organ failure and persistent SE that led to death, was described in a case report of a 3-year old (full details of both cases provided in Supplementary material). 66 A death was also noted in the patient flow figure in the study by Sanmarti et al 28 The death occurred in a child suffering from severe cerebral palsy for reasons independent of epilepsy (personal communication from author).…”

“…Indeed, as noted by Sanmarti et al, who reported aggravation in 14.7% (n ¼ 28/191) of patients, the highest in all studies, a causal link to LCM could not be demonstrated. 28 Importantly, not all patients with seizure aggravation discontinued treatment. Since data on aggravation of generalized seizures are typically based on anecdotal case reports or series, interpretation of data from such uncontrolled and retrospective studies, and particularly of case reports, must be made with caution.…”

“…Sanmarti et al did not provide separate results, but in their analysis of factors contributing to treatment response, they reported that there was a trend e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 3 ( 2 0 1 9 ) 5 8 9 e6 0 3 À !50% reduction 20% À Drowsiness, mood change (both 10%) À 100% reduction 5% À Discontinuation 0 9-month RR 65% e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 3 ( 2 0 1 9 ) 5 8 9 e6 0 3 toward focal epilepsy being associated with treatment response (odds ratio 1.83; 95%CI 0.94e3.56; p ¼ 0.074). 28 In the remaining four studies, treatment response did not differ according to seizure type. Casas-Fernandez et al noted the absence of any relationship between response and epileptic syndrome, and that two of two patients with LGS reported >50% seizure reduction.…”

“…For example, 1-year retention was 45% and 72.8% in the two largest studies, by McGinnis and Kessler, and Sanmarti et al, respectively. 27,28 Heyman et al and Gulati et al did not provide a breakdown of results according to seizure type. 33,34 In three studies, patients with focal seizures appeared to respond better to LCM than patients with generalized, or mixed seizures.…”

“…31 Sanmarti et al reported an increase in 28 (14.7%) patients, with 19 (10%) discontinuing. 28 In the study by Gulati et al, four children (10%) experienced an increase before the 3-month evaluation period and were excluded from the safety and efficacy analyses. 34 Finally, Yorns et al reported seizure aggravation in three children (7.5%), one experienced increased frequency, while the other two experienced longer seizures than usual; none discontinued treatment.…”