Systematic review and meta‐analysis: Safety of vedolizumab during pregnancy in patients with inflammatory bowel disease

Abstract

Background and Aim: Vedolizumab is a novel monoclonal antibody used in patients with inflammatory bowel disease, often affecting women of child-bearing age. We aimed to compare maternal and fetal adverse outcomes in pregnancies of women with inflammatory bowel disease exposed to vedolizumab versus those on other treatment. Methods: We performed a systematic literature search through December 2020 looking for studies including outcomes from pregnancies of female inflammatory bowel disease patients treated with vedolizumab. Our primary outcome was a composite of adverse pregnancy-related events in pregnancies of female patients on vedolizumab compared with those of disease-matched controls on other medication regimens. Events of interest included preterm births, early loss of pregnancy, late fetal death, elective termination of pregnancy, and congenital anomalies. Results: Four studies were included in our review meeting criteria for our primary analysis. Compared with those with no vedolizumab exposure, pregnancies with vedolizumab exposure had an increase in overall adverse pregnancy-related outcomes (odds ratio [OR] 2.18, 95% confidence interval [CI], 1.52-3.13). The vedolizumab group also had increased preterm births (OR 2.16, 95% CI, 1.28-3.66), and early loss of pregnancies (OR 1.79, 95% CI, 1.06-3.01) but no difference in number of live births (OR 0.60, 95%CI, 0.36-1.00), or congenital malformations (OR 1.56, 95% CI, 0.56-4.37). Conclusions: Our systematic review highlights possible concern with the general safety of vedolizumab in pregnancy, as an increase in overall total unfavorable outcomes was observed. Premature births and early loss of pregnancy were also more prevalent in pregnant female patients on vedolizumab. It is possible these findings are confounded by disease activity, and further prospective cohort studies of vedolizumab and pregnancy outcomes are warranted. contributions were as follows: Conor Bell: literature search, data entry, data interpretation and drafting of the manuscript. Parul Tandon: critical review of the manuscript. Eric Lentz: literature search, data entry, and poster creation. John K Marshall: critical review of manuscript. Neeraj Narula: study concept and design, data acquisition, data analysis and critical review of manuscript.

IBD and Motherhood: A Journey through Conception, Pregnancy and Beyond

“…However, a 2021 meta-analysis that included four studies in mothers exposed to vedolizumab suggested an increase in the odds of adverse pregnancy outcomes (OR 2.18, 95% CI 1.52-3.13) [112]. But both this study and a previous 2020 vedolizumab safety re-view concluded that disease activity, rather than medication, is likely the main factor in adverse outcomes among patients receiving anti-integrin therapy [113,114].…”

Maternal and Neonatal Outcomes in Vedolizumab- and Ustekinumab-Exposed Pregnancies: Results From the PIANO Registry

“…There was no evidence for an increased signal for placental complications in the VDZ-exposed cohort despite speculation regarding potential interference of VDZ with placental development. A meta-analysis comparing adverse pregnancy-related events in VDZ-exposed patients with disease-matched controls yielded 213 VDZ-exposed pregnancies from 4 studies and found an increase in overall adverse pregnancy–related outcomes including preterm birth and early pregnancy loss (25). On the contrary, a literature review of all publications until November 2019 yielded 5 unique studies with 284 VDZ-exposed pregnancies and found no evidence for safety concerns in the individual studies and on cumulative assessment (26).…”

Management of inflammatory bowel disease and serum level of infliximab in newborn exposed to anti-TNF therapy during pregnancy

“…Regarding the use of vedolizumab, complications such as premature rupture of membranes, pre-eclampsia, abortion, and stillbirths have been reported in up to 25% of pregnancies and neonatal complications, including prematurity, intrauterine growth retardation, and congenital malformations in up to 35% of infants from mothers exposed to the medication. [ 2 ] A more recent study [ 13 ] confirmed an increase in unfavorable outcomes, such as premature births and spontaneous abortions in pregnant women taking vedolizumab, but the results may be related to disease activity. The same results were seen in a recently published meta-analysis, [ 14 ] in which the prevalence of early pregnancy loss and preterm birth were higher in vedolizumab vs anti-TNF users.…”