Matched Analysis Finds No Link Between Dupilumab Use and Adverse Pregnancy Outcomes

An analysis of data from a large-scale study of pregnant women suggests use of dupilumab (Dupixent) was generally safe, with some evidence suggesting use may decrease the risk of adverse pregnancy outcomes relative to nonuse or use of other treatments.

A propensity-matched study of more than 700 pairs of pregnant women within the US, results indicate use of dupilumab was not associated with risk of adverse pregnancy outcomes relative to nonuse or use of other treatments among women with a multitude of conditions.

“This study represents the first larger study with a control group assessing the risk of [adverse pregnancy outcomes] associated with dupilumab treatment during pregnancy,” wrote investigators.¹ "Consistent with previous reports, no increased risk of [adverse pregnancy outcomes] was observed with dupilumab. Furthermore, this study suggests a potential decreased risk for preterm labor, gestational hypertension, pre-eclampsia and gestational diabetes compared to the control group.”

Since receiving its initial approval for the treatment of eczema in 2017, dupilumab has gone on to become one of the most widely used agents in the world, with Sanofi and Regeneron reporting more than 1,000,000 patients using the dual IL-4 and IL-13 inhibitor. After the initial approval, the FDA would go on to award subsequent label expansions for use as a treatment in the management of atopic dermatitis, chronic rhinosinusitis, asthma, eosinophilic esophagitis, COPD, and prurigo nodularis.²

Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024 by Sophie Preuß, of the Clinic for Dermatology, Allergology, and Venereology at the University Medical Center Schleswig-Holstein Lübeck, the study was designed to compare the risk of adverse pregnancy outcomes among a cohort of propensity-matched individuals identified through use of electronic health record data from the TriNetX database. For inclusion in the study, women n needed to be aged 12 to 55 years and being using dupilumab for any condition it is approved on the day of or up to 9 months after the initial coding of a pregnancy. Of note, these individuals were matched to pregnant women not using dupilumab or using other relevant systemic treatments.¹

The primary outcome of interest in the subsequent analyses was the incidence of adverse pregnancy outcomes, which included the risk of preterm labor, gestational hypertension, preeclampsia, HELLP syndrome, spontaneous abortion, gestational diabetes, and others. Investigators pointed out Hazard ratios [HR] were obtained using the Cox regression model and patients were censored at death or last follow-up.¹

In total, 702 matching pairs were identified for inclusion in the study. There were no significant differences among the groups for demographicvariables or the prevalence of smoking, obesity, diabetes mellitus, hypertension, chronic kidney disease, atopic dermatitis, asthma bronchiale, nasal polyps, prurigo nodularis, or eosinophilic esophagitis. The mean age of the dupilumab group was 31.9 (SD, 9.22) years and the mean age of the control group was 31.7 (SD, 9.29) years.¹

Results of the study revealed those in the matched control group had a greater risk of preterm labor (HR, 3.89; 95% CI, 1.60 to 9.41, P = .001), gestational hypertension without significant proteinuria (HR, 2.42; 95% CI, 1.32 to 4.45; P = .003), preeclampsia (HR, 2.36; 95% CI, 1.28 to 4.35;P = .005), and gestational diabetes (HR, 3.2; 95% CI, 1.53 to 6.70, P = .001) relative to their counterparts in the dupilumab group. Further analysis revealed the control group also had a greater risk of experiencing any adverse pregnancy outcome than those in the dupilumab group (HR, 2.76; 95% CI, 1.81 to 4.19; P <.0001).¹

However, investigators highlighted no significant differences were observed for HELLP syndrome (HR, 2.27; 95% CI, 9.44 to 11.71; P = .31) or spontaneous abortion (HR, 2.01; 95% CI, 0.88 to 4.62, P = .09) for the control group relative to the dupilumab group. Before closing investigators highlighted the retrospective nature of the study and the potential impact of unmeasured confounders limits the applicability of their findings, with calls for additional research to confirm their conclusions.¹

“To validate these findings and establish a potential causal relationship, further prospective randomized clinical trials and meta-analyses of observational cohorts are warranted,” investigators concluded.¹

References:

1. S Preuß, A Vorobyev, ME Lotta, et al. Treatment with dupilumab during pregnancy is associated with decreased risk for adverse pregnancy outcomes: A large-scale, propensity-matched retrospective cohort study. Presented at: European Academy of Dermatology and Venereology (EADV) Congress 2024. September 22 – 24, 2024. Vienna, Austria.
2. Stewart J. Dupixent (dupilumab) FDA approval history. Drugs.com. October 1, 2024. Accessed October 4, 2024. https://www.drugs.com/history/dupixent.html.