Dupilumab Shows No APO Risk During Pregnancy

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Chronic type 2 inflammatory diseases (T2IDs), such as atopic dermatitis, bronchial asthma, and eosinophilic esophagitis, affect approximately 20% of the general population and often manifest during the reproductive years.¹ During pregnancy, the maternal immune system shifts towards a Th2-dominant profile, which can exacerbate or even trigger certain T2IDs, including atopic eruption of pregnancy and bronchial asthma.² Managing these conditions effectively is essential for maternal and fetal well-being, yet treatment options are constrained due to the scarcity of therapies formally approved for use during pregnancy.

“This is the first large cohort study comparing the risk of APOs in pregnant women with and without dupilumab treatment,” researchers wrote. “We found no increased risk and even a reduced risk for some APOs in the dupilumab-treated group, supporting its safety for maternal APOs. However, as dupilumab is not approved for pregnancy, potential risks and benefits should be weighed in shared decision-making with healthcare professionals.”

Background

Dupilumab is a monoclonal antibody targeting the interleukin-4 and interleukin-13 pathways, approved for several T2ID indications. Despite its established safety in the general population, data on dupilumab exposure during pregnancy remain limited, resulting in its off-label use during this critical period. Observational reports have not demonstrated significant adverse pregnancy outcomes (APOs), but conclusive guidance remains elusive due to the absence of large-scale studies.³

Methods and Materials

To address this gap, a retrospective cohort study was conducted using the TriNetX federated health care network, which aggregates anonymized electronic health records (EHRs) from over 110 million patients. This study evaluated the incidence of APOs in pregnant women with T2IDs who were treated with dupilumab, compared with matched controls not exposed to the drug. APOs examined included preterm labor, hypertensive disorders, gestational diabetes, spontaneous abortion, intrauterine death, and puerperal infections.⁴

Results

A total of 293 pregnant women with T2IDs who received dupilumab were matched 1:1 to a non-exposed cohort. No significant increase in risk for any APO was observed in the dupilumab-treated group. Notably, the incidence of preterm labor was significantly lower in this group (3.80%) compared to controls (7.24%), with a hazard ratio (HR) of 0.11 (95% CI: 0.03–0.45; p = 0.0002). Similarly, the overall risk of experiencing any APO was lower in the dupilumab group (12.08%) versus 22.67% in the control group (HR: 0.53; 95% CI: 0.33–0.84; p = 0.0067).

Further analyses compared dupilumab-exposed pregnant women with a control group without T2ID. Again, no significant differences in APO rates were detected. However, the study found women with T2IDs—regardless of dupilumab exposure—had a significantly elevated risk of APOs compared to those without T2IDs. Specifically, bronchial asthma and atopic dermatitis were each associated with increased risks for multiple APOs. For example, asthma was linked with higher rates of hypertensive disorders, gestational diabetes, and spontaneous abortion.

Importantly, dupilumab exposure up to 6 months before pregnancy and during the postpartum period was not associated with increased maternal or fetal complications. No postpartum breast or lactation-related infections were documented in dupilumab-treated patients, further reinforcing its favorable safety profile.

This large-scale retrospective analysis strengthens the growing body of evidence supporting the safety of dupilumab during pregnancy. The findings align with smaller studies and case series that have not reported significant drug-related risks. While the retrospective design limits causal inference, the study’s robust sample size and rigorous propensity score matching provide valuable real-world insight.

Conclusion

Overall, the study found dupilumab appears to be a safe treatment option for pregnant women with T2IDs, offering potential benefits in reducing APOs such as preterm labor. These findings may help inform clinical decision-making in scenarios where treatment options are limited and disease control is essential. Nonetheless, prospective studies and continued pharmacovigilance are warranted to confirm these findings and establish definitive safety guidelines for dupilumab use during pregnancy.

References

1. Dierick BJH, van der Molen T, Flokstra-de Blok BMJ, et al. Burden and socioeconomics of asthma, allergic rhinitis, atopic dermatitis and food allergy. Expert Rev Pharmacoecon Outcomes Res. 2020;20(5):437-453. doi:10.1080/14737167.2020.1819793
2. Balakirski G, Novak N. Atopic dermatitis and pregnancy. J Allergy Clin Immunol. 2022;149(4):1185-1194. doi:10.1016/j.jaci.2022.01.010
3. Avallone G, Cavallo F, Tancredi A, et al. Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study. J EurAcad Dermatol Venereol. 2024;38(9):1799-1808. doi:10.1111/jdv.19794
4. Preuß SL, Bieber K, Vorobyev A, et al. Dupilumab shows no elevated risk for maternal adverse pregnancy outcomes: A propensity-matched cohort study. J EurAcad Dermatol Venereol. Published online April 2, 2025. doi:10.1111/jdv.20670