Safety of advanced therapies during pregnancy in women with immune-mediated inflammatory diseases: a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: No significant differences compared to anti-TNFs

• Effect Size: Major congenital malformations: 0.55% prevalence

• Primary Outcome: Live births: 82.43% pooled prevalence

• Nnt Or Sensitivity: Miscarriage rate: 8.16%; Stillbirth rate: 0.00%

• Confidence Interval: Not reported in abstract

Clinical Application

Limited by very low certainty evidence and need for individualised risk-benefit assessment Relevant to Australian rheumatologists, gastroenterologists, and obstetricians; PBS-listed advanced therapies included; requires consideration alongside TGA pregnancy categories Pregnant women with IMIDs requiring advanced therapies, particularly those on ustekinumab or vedolizumab

Abstract

BACKGROUND AND AIMS: We aimed to assess the safety of advanced therapies, excluding tumor necrosis factor inhibitors (anti-TNFs), for the treatment of immune-mediated inflammatory diseases (IMIDs), on pregnancy and neonatal outcomes. METHODS AND ANALYSIS: We performed a systematic review and meta-analysis. Study selection and data extraction were conducted independently by two reviewers. Primary outcomes included live births, major congenital malformations (MCMs), miscarriages, and stillbirths. Risk of bias was assessed using ROBINS-I, and the certainty of evidence was evaluated using GRADE. Meta-analyses of prevalence and odds ratios (ORs) comparing advanced therapies with anti-TNFs were conducted using fixed and random effect models. RESULTS: Of 14 661 manuscripts screened, 49 studies met the inclusion criteria: eight cohorts, nine case series, and 32 case reports. Most cohort studies were at a critical risk of bias. The majority of the available data related to ustekinumab (1324 exposed offspring) and vedolizumab (585 exposed offspring) whereas data on other biologics and JAK inhibitors were very limited. Pregnancies exposed to biologics had a pooled prevalence of 82.43% for live births, 0.55% for MCMs, 8.16% for miscarriage, and 0.00% for stillbirths. No significant differences in adverse pregnancy or neonatal outcomes were observed compared with women exposed to anti-TNFs. Overall, the level of evidence was very low, due largely to reliance on small observational studies and case reports. CONCLUSION: Current evidence does not suggest an increased risk of adverse pregnancy or neonatal outcomes with advanced therapies for IMIDs. However, larger, high-quality studies are needed, and these findings should be interpreted as hypothesis-generating.

References

1. 1.Pingeon, O., Grellier, N., Coulm, B., Beghin, D., Chambers, C., Chasset, F., Fautrel, B., Julsgaard, M., Restellini, S., Dechartres, A., Kirchgesner, J., & Marin, B. (2026). Safety of advanced therapies during pregnancy in women with immune-mediated inflammatory diseases: a systematic review and meta-analysis. Journal of Crohn's & Colitis. https://doi.org/10.1093/ecco-jcc/jjag045