Safety profile of monoclonal antibodies targeting the calcitonin gene-related peptide system in pregnancy: Updated analysis in VigiBase®

Abstract

Background Safety data on the use of migraine preventive monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) system in pregnancy are limited. Methods Updated pharmacovigilance assessment of the safety reports related to pregnancy associated with erenumab, galcanezumab, fremanezumab and eptinezumab, retrieved from VigiBase® as of 31 December 2021. As primary outcome, the whole group of monoclonal antibodies targeting the CGRP system was considered and sex and age subgroup disproportionality analyses using the reporting odds ratio (ROR) were conducted. Results 286 safety reports were found: 116 (40.6%) on erenumab, 125 (43.7%) on galcanezumab, 39 (13.6%) on fremanezumab, 6 (2.1%) on eptinezumab. One hundred and forty-nine (52.1%) safety reports reported only drug exposure in relation to pregnancy while 137 (47.9%) also included ≥1 pregnancy outcomes: maternal outcomes (n = 64), spontaneous abortion (n = 63), foetal growth restriction (n = 1), prematurity (n = 8), neonatal outcomes (n = 13), and poor breastfeeding (n = 1). No specific patterns of maternal, foetal and neonatal toxicity were observed. Spontaneous abortion was not disproportionally more frequently reported with erenumab, galcanezumab, fremanezumab and eptinezumab compared with the entire database (ROR 1.1, 95% confidence interval, CI, 0.8–1.5), the entire database since 2018 (ROR 1.3, 95% CI 1.0–1.8), and triptans (ROR 1.2, 95% CI 0.8–1.9). Conclusions This updated safety analysis on erenumab, galcanezumab, fremanezumab and eptinezumab in pregnancy showed no signals of foeto-maternal toxicity according to VigiBase® safety reports.

Ten open questions in migraine prophylaxis with monoclonal antibodies blocking the calcitonin-gene related peptide pathway: a narrative review

“…No deleterious effect was found in pregnant monkeys [ 166 ], but increased fetal mortality and decreased growth was found with CGRP 8 − 37 , a CGRP receptor antagonist, in pregnant rats [ 167 ]. However, no signal for an effect on the human fetus or pregnancy outcome has emerged up to now in case reports [ 168 , 169 ] or in the recently updated WHO pharmacovigilance database of 286 safety reports [ 170 ]. Although based on our abovementioned criteria the term “not recommended” could be used for anti-CGRP mAbs in pregnancy, “contraindicated” was agreed upon in Table 3 , because the exclusion of foeto-maternal toxicity may need much larger databases and follow-up of children after birth.…”