Vedolizumab clearance in neonates, susceptibility to infections and developmental milestones: a prospective multicentre population‐based cohort study

Abstract

Background:Little is known about the consequences of intrauterine exposure to, and the post-natal clearance of, vedolizumab. Aims:To investigate the levels of vedolizumab in umbilical cord blood of newborns and rates of clearance after birth, as well as how these correlated with maternal drug levels, risk of infection and developmental milestones during the first year of life Methods: Vedolizumab-treated pregnant women with inflammatory bowel disease were prospectively recruited from 12 hospitals in Denmark and Canada in 2016-2020. Demographics were collected from medical records. Infant developmental milestones were evaluated by the Ages and Stages Questionnaire (ASQ-3).Vedolizumab levels were measured at delivery and, in infants, every third month until clearance. Non-linear regression analysis was applied to estimate clearance. Results:In 50 vedolizumab-exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes. Median infant:mother vedolizumab ratio at birth was 0.44 (95% confidence interval [CI], 0.32-0.56). The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1-4.4). No infant had detectable levels of vedolizumab at 6 months of age. Developmental milestones at 12 months were normal or above average. Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28-1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60-2.77) seemed to increase the risk of infections in the offspring.Conclusions: Neonatal vedolizumab clearance following intrauterine exposure is rapid. Infant vedolizumab levels did not correlate with the risk of infections during the first year of life. Continuation of vedolizumab throughout pregnancy is safe.

Predictors of disease activity during pregnancy in women with inflammatory bowel disease—a Danish cohort study

“…Regarding the use of biologics, we found the usage twice as high in women with CD compared to women with UC, which is in line with previous studies 20,27–29 . When solely considering women with disease activity, the usage was even three times higher among women with CD as in women with UC.…”

“…A noteworthy finding in this study was a prevalence of malformations of 9.0% and 7.4% in UC and CD, respectively, that exceeds those of previous studies 20,28–31 . The congenital malformations were equally distributed between minor and major, and were categorised in different ICD classes.…”

“…Regarding the use of biologics, we found the usage twice as high in women with CD compared to women with UC, which is in line with previous studies. 20,[27][28][29] When solely considering women with disease activity, the usage was even three times higher among women with CD as in women with UC. This may reflect the fact that we continue to hold fewer remedies, that is, topical treatment, in CD as opposed to UC, and that the degree of chronicity and systemic inflammatory nature of CD may lead to more widespread use of biologics.…”

“…When assessing the presence of disease activity, we employed the Physician's Global Assessment (PGA) to define dichotomously whether or not a woman experienced disease activity. The PGA is an arbitrarily designed, multicomponent measure of disease activity that is often used in prospective studies 14,18–20 . The PGA was based on the attending gastroenterologist's assessment incorporating escalation in medical treatment, patient completion of validated disease activity indices (Harvey Bradshaw or Simple Clinical Colitis Activity Index) and if available biomarker of inflammation (C‐reactive protein [CRP] and faecal calprotectin [FC]).…”

“…The PGA is an arbitrarily designed, multicomponent measure of disease activity that is often used in prospective studies. 14,[18][19][20] The PGA was based on the attending gastroenterologist's assessment incorporating escalation in medical treatment, patient completion of validated disease activity indices (Harvey Bradshaw or Simple Clinical Colitis Activity Index) and if available biomarker of inflammation (C-reactive protein [CRP] and faecal calprotectin [FC]). The PGA was performed by only one gastroenterologist to ensure consistency in all assessments, and was applied during the pre-conception period (6 months), at conception and in each trimester of pregnancy.…”