New drugs for the treatment of IBD during conception, pregnancy, and lactation

The management of inflammatory bowel disease requires continuous medical therapy to achieve and maintain disease control. Thus, women can be exposed to different drugs during conception, pregnancy, and lactation with potentially harmful effects on the mother, foetus, or nursing infant. Conventional drugs and anti-tumour necrosis factor (TNF)-α are considered safe and can be maintained throughout all these phases. Emergent, although limited, data support safety of vedolizumab and ustekinumab, with pregnancy, as well as maternal and neonatal outcomes comparable to women unexposed or treated with anti TNF-α drugs. Placental pharmacokinetics differ between these two biologics, with an inverse infant-to-maternal ratio for vedolizumab, whereas ustekinumab shows a similar profile to anti TNF-α drugs. The clearance of vedolizumab in exposed offspring seems to be faster than anti TNF-α, estimated around 15 and 19 weeks of age, respectively. Currently, the decision to interrupt or maintain these treatments is up to physicians' judgement on a case-by-case basis. In animal studies, Janus kinase (JAK) inhibitors and ozanimod have shown embryotoxicity and teratogenicity. Moreover, tofacitinib and filgotinib seemingly affect female fertility. This review summarizes all existing data on the effects of administration of non-anti-TNF-α biologic agents and small molecules, during conception, pregnancy, and lactation.