Roberta Noseda1, Francesca Bedussi1, Claudio Gobbi2,3,4, Chiara Zecca2,3, Alessandro Ceschi1,3,5. 1. Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland. 2. Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland. 3. Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland. 4. Department of Neurology, University Hospital Basel, Basel, Switzerland. 5. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
Abstract
OBJECTIVE: To assess the safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation. METHODS: Safety reports of suspected adverse drug reactions were retrieved from VigiBase as of 31 December 2019, for a case-by-case assessment and disproportionality analysis using the reporting odds ratio (ROR). RESULTS: There were 94 safety reports: 50 (53.2%) on erenumab, 31 (33.0%) on galcanezumab, and 13 (13.8%) on fremanezumab. In five (5.3%) safety reports, drug exposure occurred prior to pregnancy, in 85 (90.4%) during pregnancy, in one (1.1%) during lactation, in one (1.1%) via paternal exposure, and in two (2.1%) the exposure time was unknown. Out of 94 safety reports, 51 (54.3%) consisted only of drug exposure, while 43 (45.7%) additionally reported 47 adverse drug reactions including maternal toxicities (n = 18), poor breastfeeding (n = 1), spontaneous abortion (n = 23), preterm birth/prematurity (n = 3), and birth defects (n = 2). There was no signal of disproportionate reporting for spontaneous abortion compared to the full database (reporting odds ratio 1.46, 95% confidence interval 0.97-2.20). When triptans were used as a comparator group, a signal of disproportionate reporting for spontaneous abortion was detected in association with erenumab, galcanezumab, and fremanezumab (reporting odds ratio 1.86, 95% confidence interval 1.12-3.13), which was not statistically significant after excluding confounded safety reports (reporting odds ratio 1.21, 95% confidence interval 0.67-2.21). CONCLUSIONS: No specific maternal toxicities, patterns of major birth defects, or increased reporting of spontaneous abortion were found. However, because of the relatively limited number of adverse drug reactions reported and the lack of long-term safety data, continuous surveillance is required in pregnant and lactating women exposed to these drugs.
OBJECTIVE: To assess the safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation. METHODS: Safety reports of suspected adverse drug reactions were retrieved from VigiBase as of 31 December 2019, for a case-by-case assessment and disproportionality analysis using the reporting odds ratio (ROR). RESULTS: There were 94 safety reports: 50 (53.2%) on erenumab, 31 (33.0%) on galcanezumab, and 13 (13.8%) on fremanezumab. In five (5.3%) safety reports, drug exposure occurred prior to pregnancy, in 85 (90.4%) during pregnancy, in one (1.1%) during lactation, in one (1.1%) via paternal exposure, and in two (2.1%) the exposure time was unknown. Out of 94 safety reports, 51 (54.3%) consisted only of drug exposure, while 43 (45.7%) additionally reported 47 adverse drug reactions including maternal toxicities (n = 18), poor breastfeeding (n = 1), spontaneous abortion (n = 23), preterm birth/prematurity (n = 3), and birth defects (n = 2). There was no signal of disproportionate reporting for spontaneous abortion compared to the full database (reporting odds ratio 1.46, 95% confidence interval 0.97-2.20). When triptans were used as a comparator group, a signal of disproportionate reporting for spontaneous abortion was detected in association with erenumab, galcanezumab, and fremanezumab (reporting odds ratio 1.86, 95% confidence interval 1.12-3.13), which was not statistically significant after excluding confounded safety reports (reporting odds ratio 1.21, 95% confidence interval 0.67-2.21). CONCLUSIONS: No specific maternal toxicities, patterns of major birth defects, or increased reporting of spontaneous abortion were found. However, because of the relatively limited number of adverse drug reactions reported and the lack of long-term safety data, continuous surveillance is required in pregnant and lactating women exposed to these drugs.
Entities:
Keywords:
Calcitonin gene-related peptide; VigiBase; adverse drug reaction; migraine