Dupilumab shows no elevated risk for maternal adverse pregnancy outcomes: A propensity-matched cohort study

Abstract

Background: Type 2 chronic inflammatory diseases (T2IDs) are highly prevalent among women of reproductive age. Dupilumab, a monoclonal antibody, is increasingly used to treat T2IDs. While dupilumab is not approved during pregnancy, smaller studies suggest no increased risk of pregnancy complications (adverse pregnancy outcomes (APOs)). Additional data are required to better assess the drug's safety during pregnancy.

Objectives: To retrospectively assess the risk of APOs in dupilumab-treated pregnant women in a large real-world database.

Methods: Pregnant women with T2ID and dupilumab treatment during pregnancy were retrieved from the US Collaborative Network of TriNetX. Pregnant women with T2ID and without dupilumab treatment served as controls. Propensity score matching (PSM) for demographics, diagnoses, medications and putative APO risk factors was employed. Outcomes analysed included various maternal pregnancy complications, including premature obstetric labour, pregnancy-induced hypertension, gestational diabetes, puerperal infections and spontaneous abortion. Survival analyses were assessed using the Kaplan-Meier method, outcome differences the log-rank test and hazard ratios (HR) the Cox regression model.

Results: During pregnancy, 293 women were exposed to dupilumab. Following PSM, no increased risks for APOs were noted. Of note, reduced risks for premature obstetric labour (HR: 0.11, confidence interval (CI): 0.03-0.45, p = 0.0002) and 'any APO' (HR: 0.53, CI: 0.33-0.84, p = 0.0067) in the dupilumab-treated group were found. Furthermore, no difference in risks for any APO was noted between dupilumab-treated and untreated women up to 6 months before pregnancy or during the postpartum period.

Conclusions: This large-scale propensity-matched retrospective cohort study suggests a favourable safety profile of dupilumab during pregnancy. Given the difficulties of prospective studies during pregnancy, it provides valuable insights, though further studies are needed to confirm these findings and explore causal relationships.

FIGURE 1

Graphical representation of the study design structure.

FIGURE 2

(a) Risk of adverse pregnancy outcomes (APOs) in patients with dupilumab treatment during pregnancy and controls. Points indicate hazard ratios (HR), error bars correspond to the confidence interval (CI). Patients with the outcome prior to the index event were excluded, resulting in different group sizes for each outcome. *To protect patient privacy, numbers are rounded up to 10. (b) Nelson Aalen Plot contrasting the risk of ‘any APO’ in patients with dupilumab treatment during pregnancy and controls. Outcomes up to 270 days after the index event (pregnancy with or without dupilumab treatment) are shown. Data are based on 293 electronic health records (EHRs) for cases and propensity‐matched controls. (c) Nelson Aalen Plot contrasting the risk of preterm labour in patients with dupilumab treatment during pregnancy and controls. Outcomes up to 270 days after the index event (pregnancy with or without dupilumab treatment) are shown. Data are based on 293 EHRs for cases and propensity‐matched controls.

FIGURE 3

Risk of adverse pregnancy outcomes (APOs) in patients with dupilumab treatment and T2ID compared to controls without dupilumab treatment and without T2ID. Points indicate hazard ratios (HR), error bars correspond to the confidence interval (CI). Patients with the outcome prior to the index event were excluded. Data are based on 283 electronic health records (EHRs) for cases and propensity‐matched controls. *To protect patient privacy, numbers are rounded up to 10.

FIGURE 4

Risk of adverse pregnancy outcomes (APOs) in patients with T2IDs compared to controls without any T2ID. Points indicate hazard ratios (HR), error bars correspond to the confidence interval (CI). Patients with the outcome prior to the index event were excluded.

FIGURE 5

Risk of adverse pregnancy outcomes (APOs) in patients with dupilumab treatment 6 months to 1 day before pregnancy and controls. Points indicate hazard ratios (HR), error bars correspond to the confidence interval (CI). Patients with the outcome prior to the index event were excluded. Data are based on 243 electronic health records (EHRs) for cases and propensity‐matched controls. *To protect patient privacy, numbers are rounded up to 10.

FIGURE 6

Risk of adverse pregnancy outcomes (APOs) in patients with dupilumab treatment during pregnancy or postpartum and controls. Points indicate hazard ratios (HR), error bars correspond to the confidence interval (CI). Patients with the outcome prior to the index event were excluded. Data are based on 300 electronic health records (EHRs) for cases and propensity‐matched controls. *To protect patient privacy, numbers are rounded up to 10.