Editorial: ustekinumab during pregnancy ‐ reassuring but still not enough

In a French populationbased study of 36,654 pregnancies in women with inflammatory bowel disease (IBD), active disease during pregnancy was associated with increased rates of stillbirth, preterm birth, small for gestational age, caesarean section and pregnancyrelated hospitalisation.1 The European Cohn's and Colitis guidelines (ECCO) have an updated consensus on pregnancy management.2 According to ECCO, IBD remission should be achieved at least 6 months before conception and maintained throughout pregnancy. The use of Immunoglobulin G1based monoclonal antibodies has raised many concerns during the last two decades considering foetal exposure from the second trimester. AntiTNF prescription during pregnancy appears to be safe for mothers and children who have been exposed in utero to antiTNF compared to unexposed mothers and children.1,3,4 However, live attenuated vaccines should not be administered within the first year of life in children exposed in utero to biological agents.2 ECCO recommends continuing antiTNF treatment throughout pregnancy for women with active and remitting disease. The use of nonTNF biological agents such as ustekinumab and vedolizumab is more questionable considering limited experience during pregnancy. However, ECCO recommends to continue nonantiTNF biological agents throughout pregnancy for women with active disease just before or during pregnancy, or with disease that is difficult to control.2 However, it is unclear as to whether ustekinumab and vedolizumab should be continued during pregnancy in women in remission. In a multicentre, prospective, cohort study, AvniBiron et al presented data on 27 pregnant women with IBD treated with ustekinumab and matched 1:2 to controls treated with an antiTNF agent (n = 52) or nonbiological therapy (n = 50).5 Pregnancy, neonatal and newborn outcomes were similar in the three groups. Ustekinumab appeared safe for mothers, foetus and newborns. Given the limited number of reported cases of pregnancy with ustekinumab, any new data on this issue are welcome. A pooled analysis of 408 maternal ustekinumabexposed pregnancies from the manufacturer's global safety database showed similar pregnancy and neonatal outcomes compared with the US general population.6 The study of AvniBiron et al is limited by its small sample size and lack of adjustment for confounding factors. Future, large prospective studies are needed to demonstrate the safety of nonantiTNF biological agents on pregnancy and neonatal outcomes compared to antiTNF agents.