Authors :
Presenting Author: Piero Perucca, MD, PhD, FRACP – The University of Melbourne and Bladin-Berkovic Comprehensive Epilepsy Program, Austin Health, Melbourne, Australia
P Emanuela Voinescu, MD, PhD – Brigham and Women's Hospital, Harvard Medical School, Boston, USA; Lata Vadlamudi, MBBS, PhD, FRACGP, FRACP – University of Queensland Centre for Clinical Research (UQCCR), Royal Brisbane and Women’s Hospital, Brisbane, Australia; Dimitrios Bourikas, PhD, MSc – UCB Pharma, Alimos, Greece; Daya Chellun, MD – UCB Pharma, Braine-l'Alleud, Belgium; Konrad Werhahn, MD, PhD – UCB Pharma, Monheim am Rhein, Germany; Thomas Kumke, PhD – UCB Pharma, Monheim am Rhein, Germany; Bettina Schmitz, MD – Vivantes Humboldt-Klinikum, Berlin, Germany
Rationale:
In pregnancy, the risks of uncontrolled epileptic seizures to the mother and fetus need to be balanced against the potential teratogenic effects of antiseizure medications (ASMs). Data are limited on pregnancy outcomes among patients taking lacosamide (LCM). The objective of the current analysis was to evaluate fetal outcomes of LCM-exposed pregnancies.
Methods:
This analysis was of all prospective reports (available in the UCB Pharma global safety database [cutoff 31 Aug 2021]) of exposure to LCM during pregnancy from spontaneous sources (routine clinical settings) or solicited reports from interventional clinical studies and non-interventional post-marketing studies (excluding data from registries and published data from NIS and non-UCB Pharma studies). Reports were classified as prospective if the pregnancy was ongoing, the pregnancy outcome was unknown, or no abnormality regarding fetal health was reported at the time of initial notification. Monotherapy was reported if the patient received LCM monotherapy throughout the entire pregnancy.
Results:
Overall, 213 cases of pregnancy with known outcomes were identified; 202 were individual maternal exposure pregnancies. Among pregnancies with maternal exposure, there were 204 reported pregnancy outcomes (two twin pregnancies in the polytherapy group). During pregnancy, 21.8% (44/202) patients received LCM as monotherapy, and 78.2% (158/202) received polytherapy. At the start of pregnancy, mean age was 29.0 (SD: 7.1) and 28.2 (SD: 6.0) years for patients on LCM monotherapy and polytherapy, respectively (Table 1). Overall, 88.6% (39/44) of patients on LCM monotherapy and 90.5% (143/158) on LCM polytherapy received LCM during the first trimester, at a mean maximum dose of 352.9 (SD: 191.9) mg/day and 297.6 (SD: 119.1) mg/day, respectively (Table 1). A total of 57.0% (90/158) of patients on LCM polytherapy were on one concomitant ASM and 41.8% (66/158) were on ≥2 concomitant ASMs (2 unknown; Table 1). The most common concomitant ASMs were levetiracetam (51.9% [81/156]) and lamotrigine (27.6% [43/156]). Among pregnancy outcomes with maternal exposure to LCM as monotherapy vs polytherapy, the proportion of live births was numerically higher (84.1% [37/44] vs 76.3% [122/160]), and the proportion of all abortions was numerically lower (15.9% [7/44] vs 22.5% [36/160]; Table 2). Congenital malformations were reported in 2.3% (1/44) and 6.9% (11/160) of pregnancy outcomes (based on all known outcomes) with maternal exposure to LCM monotherapy and polytherapy, respectively. Preterm delivery was reported in 10.8% (4/37) and 9.0% (11/122) of live births with maternal exposure to LCM monotherapy and polytherapy, respectively; small for gestational age was reported in 2.7% (1/37) and 2.5% (3/122) of live births; and low birth weight (<2500g or if reported as such) was reported in 13.5% (5/37) and 8.2% (10/122) of live births (Table 2).
Conclusions:
Most LCM-exposed pregnancies resulted in healthy live births. No new safety concerns were identified. Additional data are needed to fully evaluate the safety of LCM in pregnancy.
Funding:
UCB Pharma-sponsored