Optimal Choice of Biologics and Small Molecules for Treating Women of Childbearing Age with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, commonly affects women of reproductive age. Therefore, the safety of therapeutic agents during pregnancy and lactation is a major clinical concern. Among available treatments, anti-tumor necrosis factor (TNF) agents are the most extensively studied, and recent large cohort studies and meta-analyses have demonstrated no significant increase in adverse outcomes such as miscarriage, preterm birth, congenital malformations, or neonatal infections with continued use during pregnancy. Evidence for newer biologics, including the anti-integrin agent vedolizumab and the anti-interleukin-12/23 agent ustekinumab, is more limited but increasingly reassuring, with population-based studies and registry data indicating safety profiles comparable to those of anti-TNF agents. In contrast, small molecule agents, such as Janus kinase (JAK) inhibitors (tofacitinib, filgotinib, upadacitinib) and sphingosine-1-phosphate (S1P) receptor modulators (ozanimod), raise greater concern due to their low molecular weight, potential for placental transfer, and teratogenic findings in animal studies, while human data remain scarce. Current international guidelines, including European and Australian consensus statements, recommend discontinuation of these small molecules prior to conception and avoidance during pregnancy and breastfeeding. In summary, current evidence supports the relative safety of biologics, particularly anti-TNF agents, for use during pregnancy in patients with IBD, while newer biologics require further confirmation, and small molecules are not recommended. Treatment decisions should be individualized, balancing maternal disease control, fetal safety, and patient preference to optimize outcomes in pregnant women with IBD.