Abstracts

Rationale: Lacosamide (LCM) has been approved as adjunctive therapy for patients with focal epilepsy since 2008. The objective of this project was to evaluate pregnancy outcomes in women exposed to LCM during pregnancy using data from the UCB global safety database. Methods: The global safety database was searched for pregnancy reports up to Oct 2015. Reports from pregnancy registries were excluded. Pregnancies were classified at the time of the initial reporting as prospective if they were ongoing with no reported abnormal findings, and as retrospective if an abnormality had been detected or the pregnancy had ended. Given the well-established bias toward adverse outcomes and lack of a denominator for calculations in retrospective reports, only results for prospective reports are presented here. Data were evaluated by two independent reviewers. Results: In total, 263 pregnancies were reported (13 paternal exposures are not described here; Figure 1). Of the 250 maternal exposures, outcomes were known for 154 (61.6%), of which 101 (65.5%) were prospective, mostly reported spontaneously (70/101, 69.3%) from Europe and North America (81/101, 80.2%). Among women with available data (n=62), mean age at estimated delivery date was 30.1 (±5.8) and 77.4% were aged 18–34 years. During pregnancy, LCM was used as monotherapy by 15.8% (16/101) and as adjunctive therapy by 83.2% (84/101) of women (1% unknown). Among women on polytherapy during pregnancy, 16.8%, 47.5% and 35.6% were taking 1, 2 and ≥3 concomitant AEDs, respectively, with the most frequently reported being levetiracetam (38.0%), lamotrigine (34.5%) and carbamazepine (21.4%). Most pregnancies resulted in live births (n=75; 74.3%), including 14 of the 16 pregnancies exposed to LCM monotherapy (87.7%). Most neonates were normal with respect to term, gestational age at outcome and birth weight (Table 1). Of the 69 live births with detailed exposure data, most pregnancies were exposed during the first trimester (n=66), including the 14 monotherapy live births. Teratology review revealed 6 cases of malformation; no discernible patterns were identified, and with a single exception, all occurred with polytherapy. Conclusions: Most prospective maternal exposure reports resulted in healthy live births. Six cases of malformation (5 with polytherapy) were reported; however, Interpretation of these results is limited by the lack of a comparator group, and further confounded by the use of concomitant AEDs known to cause fetal abnormalities in some reported cases. Direct comparisons with malformation rates in the general population (approximately 2–4%; http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071639.pdf Accessed 26 Sep 2016), or in other populations cannot be made due to the nature of safety reporting. Given these limitations and the small sample size, conclusions on the potential risk of malformation due to LCM exposure during pregnancy cannot be drawn and collection of further monotherapy data is required. Funding: UCB Pharma-sponsored