Placental MadCAM1 Expression and Potential Consequences for the Treatment with Vedolizumab during Pregnancy

Zelinková, Zuzana; Berakova, Katarina; Podmanicky, Dusan; Kadleckova, Barbora

doi:10.1016/s0016-5085(17)32653-7

Cited by 8 publications

(3 citation statements)

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“…This is probably due to the higher number of patients with active disease in the VDZE group since the difference in live born infants between both groups disappeared after excluding patients with active disease in pregnancy. Since MAdCAM‐1 is expressed in the human placenta during the first trimester of pregnancy, concerns have been raised about a theoretical risk of early miscarriage with the use of VDZ during conception and pregnancy. However, in this cohort of 79 VDZ‐exposed pregnancies, there was no significant difference in the number of miscarriages between the VDZE group and the TNFE or CON IBD group.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti‐TNF or conventional therapy: results of the European CONCEIVE study

Moens¹,

Woude²,

Julsgaard³

et al. 2019

Aliment Pharmacol Ther

102

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Summary Background Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab‐exposed pregnancies (VDZE) are sparse. Aims To assess pregnancy and child outcomes of VDZE pregnancies and to compare these results to anti‐TNF exposed (TNFE) or both immunomodulatory and biologic unexposed (CON IBD) pregnancies. Methods A retrospective multicentre case‐control observational study was performed. Results VDZE group included 79 pregnancies in 73 IBD women. The TNFE and CON IBD group included 186 pregnancies (162 live births) in 164 IBD women and 184 pregnancies (163 live births) in 155 IBD women, respectively. At conception, cases more often had active disease ([VDZE: 36% vs TNFE: 17%, P = .002] and [VDZE: 36% vs CON IBD: 24%, P = .063]). No significant difference in miscarriage rates were found between groups (VDZE and TNFE: 16% vs 13%, P = .567; VDZE and CON IBD: 16% vs 10%, P = .216). In live‐born infants, median gestational age and birthweight were similar between groups. Median Apgar score at birth was numerically equal. Prematurity was similar in the VDZE group compared to the control groups, even when correcting for disease activity during pregnancy. The frequency of congenital anomalies was comparable between groups as were the percentages of breastfed babies. During the first year of life, no malignancies were reported and infants' infection risk did not significantly differ between groups. Conclusion No new safety signal was detected in VDZE pregnancies although larger, prospective studies are required for confirmation.

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Section: Discussionmentioning

confidence: 99%

Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti‐TNF or conventional therapy: results of the European CONCEIVE study

Moens¹,

Woude²,

Julsgaard³

et al. 2019

Aliment Pharmacol Ther

102

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“…Vedolizumab is a humanized monoclonal antibody, which prevents leukocyte trafficking to the gut by inhibiting the binding of a4b7 integrin to mucosal vascular addressin cell adhesin molecule 1 (MAdCAM-1) (15). While MAdCAM-1 is primarily located in gastrointestinal lymphoid tissue, it has been identified in human placental vessels and was demonstrated to play an integral role in placenta development (16,17). Ustekinumab is a humanized monoclonal IgG1 targeting the p40 subunit of interleukin (IL)-12 and IL-23, preventing their interaction with cell surface receptors and production of inflammatory cytokines (12,18).…”

Section: Introductionmentioning

confidence: 99%

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

Chugh,

Long,

Jiang

et al. 2023

Am J Gastroenterol

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Background Pregnancy outcomes in inflammatory bowel disease (IBD) patients with quiescent disease are similar to the general population. Data from the Pregnancy Inflammatory bowel disease And Neonatal Outcomes (PIANO) registry have demonstrated the safety of anti-tumor necrosis factor alpha (TNFs) agents and thiopurines in pregnancy. The objective of this study was to provide information from the PIANO registry on maternal and fetal outcomes in patients exposed to the newer biologics ustekinumab (UST) and vedolizumab (VDZ). Methods In this multicenter prospective observational study, we included pregnant women with singleton pregnancies and a diagnosis of IBD. Questionnaires were administered to women at study intake, each subsequent trimester, delivery, and at 4, 9, and 12 months after birth. Bivariate analyses were utilized to determine the independent effects of specific drug classes on outcomes. The exposure cohorts were VDZ, UST, anti-TNFs, immunomodulators, and combination with anti-TNFs and immunomodulators. All were compared to no exposure and to biologics/immunomodulators. Results There were 1669 completed pregnancies with 1610 live births. Maternal mean age was 32.1 (SD 4.6) years at delivery with 66 VDZ and 47 UST exposed. Women on UST were more likely to have Crohn’s disease. There was no increased risk of spontaneous abortion, small for gestational age, low birth weight, neonatal intensive care unit stay, congenital malformations, or intrauterine growth restriction with in utero VDZ or UST exposure. The rate of preterm birth was lower (0.0%) for UST-exposed as compared to other groups including VDZ (13.8%), anti-TNF (8.2%), combination therapy (14.2%), immunomodulator (12.3%), and unexposed (9.7%)(p = 0.03). Rates of serious infections at birth, 4 months, and within the first 12 months of life were comparable among all groups. Nonserious infections were lower at 12 months in UST exposed pregnancies. There was no increased risk signal for placental complications in the VDZ cohort. UST infant concentrations at birth were increased whereas VDZ concentrations were overall decreased compared to maternal serum drug concentration. Conclusion This analysis of UST and VDZ exposure during pregnancy suggests no increase in complications compared to TNFs, immunomodulators and combination TNFs/immunomodulators. No signal was found for increased placental events with either therapy. Continuation of UST and VDZ throughout pregnancy is recommended.

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“…19 Interestingly, MAdCAM-1 is also expressed within the placenta, and therefore, the use of VDZ during pregnancy has raised concern about effects on placental function. 20 Recent studies have reported on the safety of VDZ during pregnancy. 3,[21][22][23][24][25][26][27][28][29][30] However, these studies are often limited by small-sample sizes and lack of standardized control groups.…”

Section: Introductionmentioning

confidence: 99%

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

Bell

Tandon

Lentz

et al. 2021

J of Gastro and Hepatol

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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.

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Placental MadCAM1 Expression and Potential Consequences for the Treatment with Vedolizumab during Pregnancy

Cited by 8 publications

References 0 publications

Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti‐TNF or conventional therapy: results of the European CONCEIVE study

Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti‐TNF or conventional therapy: results of the European CONCEIVE study

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

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

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