Vedolizumab clearance in neonates, susceptibility to infections and developmental milestones: a prospective multicentre population-based cohort study
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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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Alimentary Pharmacology and Therapeutics |
| Vol/bind | 54 |
| Udgave nummer | 10 |
| Sider (fra-til) | 1320-1329 |
| Antal sider | 10 |
| ISSN | 0953-0673 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
This investigator-initiated study was supported by unrestricted grants from the Health Research Fund of the Central Denmark Region, the Danish Crohn's & Colitis Foundation, the AP Moeller Foundation of the Advancement of Medical Science, and Takeda Pharma A/S (grant no. IISR-2017-102375). The external funders had no involvement in any aspect of the study and writing of the report. The authors thank the women and infants who participated in this study, the external funders, and the members of the NOVA study group. Declaration of personal interests: Mette Julsgaard has served on the advisory board of Tillotts, and has received speaker?s fees from MSD, Ferring, and Takeda; Has received a research grant from Takeda for the present study (Takeda had no role in design, implementation or interpretation of the study). Daniel C Baumgart has served on scientific advisory boards with AbbVie, Gilead, Janssen, Merck, Amgen, Pfizer, and Takeda. All honoraria were collected by the University of Alberta. Jens Kjeldsen has received speaker?s fees from Takeda, and Tillotts. Signe Wildt has served on the advisory boards of MSD, Takeda and Tillotts, and has received consultants fee from Tillotts and speaker?s fees from Takeda. Petra Weimers has received consulting fees from Vifor Pharma Nordiska AB, grants from Ferring l?gemidler and Tillotts Pharma AG, as well as non-financial support from Janssen-Cilag A/S, Calpro AS, Pharmacosmos A/S and Vifor Pharma Nordiska AB. Kent V Haderslev has received speaker?s fees from MSD, Takeda, and Janssen. J?rn Brynskov has served on advisory boards of Abbvie, Janssen, Pfizer, Gilead, MSD, and has received speaker?s fee from Takeda and MSD. S?ren Lyhne has received consulting fee from Takeda. Christian L. Hvas has received has received speaker?s fees from Takeda, and Tillotts. Jens Kelsen has served on the advisory board of Gilead, Takeda and Janssen and has received speaker?s fee from Pfizer. The remaining authors disclose no conflicts. Funding information: This investigator-initiated study was supported by unrestricted grants from the Health Research Fund of the Central Denmark Region, the Danish Crohn?s & Colitis Foundation, the A.P. Moeller Foundation of the Advancement of Medical Science, and Takeda Pharma A/S (grant no. IISR-2017-102375). The external funders had no involvement in any aspect of the study and writing of the report.
Funding Information:
Mette Julsgaard has served on the advisory board of Tillotts, and has received speaker’s fees from MSD, Ferring, and Takeda; Has received a research grant from Takeda for the present study (Takeda had no role in design, implementation or interpretation of the study). Daniel C Baumgart has served on scientific advisory boards with AbbVie, Gilead, Janssen, Merck, Amgen, Pfizer, and Takeda. All honoraria were collected by the University of Alberta. Jens Kjeldsen has received speaker’s fees from Takeda, and Tillotts. Signe Wildt has served on the advisory boards of MSD, Takeda and Tillotts, and has received consultants fee from Tillotts and speaker’s fees from Takeda. Petra Weimers has received consulting fees from Vifor Pharma Nordiska AB, grants from Ferring lægemidler and Tillotts Pharma AG, as well as non‐financial support from Janssen‐Cilag A/S, Calpro AS, Pharmacosmos A/S and Vifor Pharma Nordiska AB. Kent V Haderslev has received speaker’s fees from MSD, Takeda, and Janssen. Jørn Brynskov has served on advisory boards of Abbvie, Janssen, Pfizer, Gilead, MSD, and has received speaker’s fee from Takeda and MSD. Søren Lyhne has received consulting fee from Takeda. Christian L. Hvas has received has received speaker’s fees from Takeda, and Tillotts. Jens Kelsen has served on the advisory board of Gilead, Takeda and Janssen and has received speaker’s fee from Pfizer. The remaining authors disclose no conflicts.
Funding Information:
This investigator‐initiated study was supported by unrestricted grants from the Health Research Fund of the Central Denmark Region, the Danish Crohn’s & Colitis Foundation, the A.P. Moeller Foundation of the Advancement of Medical Science, and Takeda Pharma A/S (grant no. IISR‐2017‐102375). The external funders had no involvement in any aspect of the study and writing of the report.
Funding Information:
This investigator‐initiated study was supported by unrestricted grants from the Health Research Fund of the Central Denmark Region, the Danish Crohn's & Colitis Foundation, the AP Moeller Foundation of the Advancement of Medical Science, and Takeda Pharma A/S (grant no. IISR‐2017‐102375). The external funders had no involvement in any aspect of the study and writing of the report.
Publisher Copyright:
© 2021 John Wiley & Sons Ltd.
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