Safety profile of Dupilumab during pregnancy: a data mining and disproportionality analysis of over 37,000 reports from the WHO individual case safety reporting database (VigiBase™)

Atopic dermatitis, known also as atopic eczema, represents a commonly diagnosed, chronic or recurrent/relapsing inflammatory disorder. From a clinical point of view, it is characterized by acute flare-ups of intense itching, eczematous pruritic lesions involving dry skin. Dupilumab is the only biologic agent approved to treat moderate to severe course of atopic dermatitis, which can be particularly severe during pregnancy causing distress and impacting on maternal and fetal health. However, there is a dearth of data concerning the safety profile of Dupilumab during gestation. Therefore, we took advantage of a large global pharmacovigilance database. From inception up to March 9, 2021, 94,065 adverse drug reactions (ADRs) from 37,848 unique reports were retrieved. Of these, 36 reports related to pregnancy, puerperium and perinatal ADR could be extracted from the pharmacovigilance database. More than half of reports (n = 21; 58.3%) were spontaneous abortion, followed by other events, including exposure to the drug during the pregnancy (n = 8; 22.2%). Two cases of abortion were reported. No studied pregnancy, puerperium and perinatal ADR was found to be associated with the use of Dupilumab. The only OR significantly greater than 1 was the OR associated with the risk of developing heterotopic pregnancy (21.66 [95% CrI 2.95-159.02]) even if the IC was highly imprecise (1.45 [95% CrI from -2.34 to 3.09]), probably because of the single case of heterotopic pregnancy reported. In conclusion, Dupilumab use appears safe during gestation. Further studies are needed, especially to better understand the mechanisms underlying the pharmacological actions and ADR of Dupilumab.