Safety of vedolizumab and ustekinumab in the treatment of pregnant women with inflammatory bowel disease – a multicentre retrospective-prospective observational study

Background: Inflammatory bowel disease (IBD) is mostly diagnosed in young women of fertile age, and a significant number of patients become pregnant while they have the disease. The remission of the illness, which is often achieved by intensive anti inflammatory treatment, has been found to be the most important factor of a successful pregnancy. Vedolizumab (VDZ) and ustekinumab (UST) are newer types of monoclonal antibodies with different mechanisms of effect when compared to anti-TNF treatment. VDZ is a monoclonal antibody against the α4ß7 integrin receptor, and UST against interleukin 12/23; both have expanded the spectrum of the biological treatment of IBD in recent years. Aims: To present the results of a multicentre observational study. The primary aim was to assess the safety of vedolizumab and ustekinumab for pregnancy, foetal development and the neonatal outcome. The secondary aim was to measure the drug concentration in maternal and cord blood at the time of delivery. Methods: It was a multicentre, retrospective-prospective observational study. Data on patients’ demographics, clinical characteristics and pregnancy were collected by the treating physician using a predefined questionnaire, data on newborn outcome were obtained from medical documentation. The ELISA method was used to measure the VDZ and UST concentrations. Results: The study took place in 15 IBD clinical centres in the Czech Republic. 79 women with 85 completed pregnancies were included in the study, and they were exposed to VDZ or UST during pregnancy. 36 women were treated with vedolizumab (median age 32 years) and 49 with ustekinumab (median age 30.5 years). In the group with VDZ, live births occurred with 32 women (88.9%), and there were two early spontaneous abortions up to the eighth week of gestation in addition to two instrumentally aborted pregnancies (4, 11.1%). 31 children (93.9%) in the group with VDZ were born at term with a median birth weight of 3,097.5 grams. In the ustekinumab group, 39 women (79.6%) had live births, there were nine early abortions and one instrumentally aborted pregnancy (10, 20.4%). 38 (97.4%) children were born at term with a median birth weight of 3,265 grams. The drug levels of VDZ and UST at birth were measured in 44 neonate-mother pairs (21 VDZ, 23 UST). The median level of VDZ in maternal venous blood was 7.2 mg/l, and in cord blood it was 4.7 mg/l (infant / maternal ratio 0.66). With UST, the median maternal level was 4.7 mg/l, and in neonates it was 7.9 mg/l (infant / maternal ratio 1.65). Conclusion: The results found in a group of women that were being treated for IBD and were exposed to at least one dose of biologic treatment with UST or VDZ during pregnancy are consistent with previously published evidence showing no adverse events, and they confirm the safety profile of new biologics in pregnancy. Due to the still limited number of enrolled patients, further studies are needed on the outcomes of pregnancies with new biologics drugs. Keywords vedolizumab, ustekinumab, pregnancy, transplacentární přenos