Pregnancy safety of biologics in inflammatory bowel disease: A systematic review and network meta-analysis

Biologic safety during pregnancy in patients with inflammatory bowel disease (IBD) remains a clinical concern, particularly with the increasing use of novel agents such as ustekinumab (UST) and vedolizumab (VDZ).

A network meta-analysis (NMA) was performed to compare pregnancy-related outcomes among various biological agents and nonbiologic-exposed patients.

Systematic review and frequentist random-effects NMA of comparative observational studies.

This study systematically searched from inception to 23 March 2025 for comparative studies reporting pregnancy outcomes in biologics or conventional therapies (CT)-exposed patients with IBD. Outcomes included preterm birth, congenital malformation (CM), low birth weight (LBW), and spontaneous abortion. An NMA model was applied. Subgroup analysis was conducted for studies with comparable baseline disease activity between the treatment groups.

This NMA included 12 studies. Anti-tumor necrosis factor alpha (TNF-α) agents were not associated with an increased risk of any adverse pregnancy outcomes. UST and VDZ were associated with increased CM risks (UST: odds ratio [OR]: 2.32 [1.31-4.10]; VDZ: OR: 1.98 [1.11-3.52]), and VDZ was associated with LBW (OR: 2.17 [1.15-4.11]). These associations were not significant in the subgroup analyses limited to studies with similar disease activity. Sensitivity analysis revealed that a single important study influenced the CM risk of UST/VDZ, whereas the LBW risk with VDZ remained consistent.

This is the first NMA to comprehensively assess the pregnancy-related safety of biologic therapies, including the novel biologics VDZ and UST, in patients with IBD. Anti-TNF agents have the most robust pregnancy safety evidence and were not associated with an increased risk of adverse pregnancy outcomes in this analysis. The findings for UST and VDZ should be framed as exploratory and potentially affected by residual confounding, as the observed risk signals were not consistently maintained in the additional analyses.

INPLASY202540012.