Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease

Abstract

Summary Background Vedolizumab is a gut‐selective immunoglobulin G1 monoclonal antibody to α4β7 integrin for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Prospective clinical studies of vedolizumab in pregnancy have not been conducted; therefore, existing safety data of vedolizumab in pregnancy were examined. Aim To assess pregnancy outcomes in females and partners of males who received vedolizumab. Methods All pregnancy data collected during the clinical programme (from 14 May 2007 to 27 June 2013) and in the post‐marketing setting (to 19 November 2015) were analysed. Results Across six studies, there were 27 pregnancies in female participants and 19 pregnancies in partners of male participants. Among 24 vedolizumab‐treated females (23 with CD/UC, one healthy volunteer), there were 11 live births, five elective terminations, four spontaneous abortions and four undocumented outcomes. A congenital corpus callosum agenesis anomaly was reported in one live birth from a healthy volunteer with extensive obstetric history exposed to single‐dose vedolizumab 79 days before estimated conception. Of 19 pregnancies in partners of male participants, there were 11 live births, two spontaneous abortions, three elective terminations and three undocumented outcomes. Post‐marketing reports recorded 81 pregnancies, resulting in four live births, 11 spontaneous abortions and 66 pregnancies that were on‐going or reported undocumented outcomes. Conclusions Initial analysis, limited by sample size and follow‐up, identified no new safety concerns for pregnancy outcomes in females directly or indirectly exposed to vedolizumab. However, vedolizumab should be used during pregnancy only if the benefits to the mother outweigh the risks to the mother/unborn child.

Immunogenicity is not the driving force of treatment failure in vedolizumab‐treated inflammatory bowel disease patients

“…This finding is particularly relevant for female IBD patients who are pregnant during vedolizumab therapy. When being in the second trimester of pregnancy, vedolizumab therapy is usually discontinued because of the potential risks for the unborn child . As AVA do not increase upon stop of therapy, pregnant patients can discontinue treatment without the risk of developing AVA, which may reduce the probability of regaining a clinical response when resuming vedolizumab therapy.…”

Care of the Pregnant Patient With Inflammatory Bowel Disease

“…However, among 24 vedolizumab-treated women, there were 12 live births, five elective terminations, and four spontaneous abortions. 70 Women are currently being enrolled in the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes registry and will provide additional long-term safety data of vedolizumab exposure in pregnancy.…”

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

“…By blocking this interaction, VDZ inhibits the trafficking of gut‐homing lymphocytes . However, data on the use of VDZ during conception and pregnancy remain sparse . We previously reported several pregnancy and neonatal complications among female IBD patients treated with VDZ in a retrospective Belgian study.…”

“…In particular, a relatively high number of congenital malformations were reported (three out of 23 live births: hip dysplasia, pulmonary valve stenosis and Hirschsprung's disease). Additionally, the published case of a congenital corpus callosum agenesis anomaly in a healthy volunteer exposed to VDZ gave rise to concerns . Since the Belgian study was too small to draw firm conclusions and underlying active disease was a major confounding factor, a pan‐European study was performed to increase the number of VDZ‐exposed (VDZE) pregnancies and thus the statistical power.…”