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Use of Biologic Therapy by Pregnant Women With Inflammatory Bowel Disease Does Not Affect Infant Response to Vaccines

https://doi.org/10.1016/j.cgh.2017.08.041Get rights and content

Background & Aims

In women with inflammatory bowel diseases (IBDs), exposure to immunomodulator or biologic therapy has not been associated with adverse events during pregnancy or outcomes of newborns. We investigated whether exposure of patients to these agents during pregnancy affects serologic responses to vaccines in newborns.

Methods

We collected data from the Pregnancy in IBD and Neonatal Outcomes registry, which records outcomes of pregnant women with diagnosis of IBD receiving care at multiple centers in the United States, from 2007 through 2016. Serum samples collected from infants at least 7 months old were analyzed for titers of antibodies to Haemophilus influenzae B (HiB) or tetanus toxin; mothers completed a survey of vaccine practices and outcomes from July 2013 through October 2016. Umbilical cord blood samples from 33 infants were assayed for concentration of biologic agents. Vaccination response was compared between infants born to mothers exposed to biologic therapy (infliximab, adalimumab, certolizumab pegol, golimumab, natalizumab, vedolizumab, or ustekinumab—either as a single agent or in combination with an immunomodulator, at any time between conception and delivery) and infants born to unexposed mothers.

Results

A total of 179 women completed the vaccine survey (26 biologic unexposed, 153 exposed to a biologic agent). We found no significant difference in proportions of infants with protective antibody titers against HiB born to exposed mothers (n = 42, 71%) vs unexposed mothers (n = 8, 50%) (P = .41). We also found no difference in the proportion of infants with protective antibody titers to tetanus toxoid born to exposed mothers (80%) vs unexposed mothers (75%) (P = .66). The median concentration of infliximab in cord blood did not differ significantly between infants with vs without protective antibody titers to HiB (P = .30) or tetanus toxoid (P = .93). Mild reactions were observed in 7/40 infants who received rotavirus vaccine and whose mothers had been exposed to biologic therapies.

Conclusions

Vaccination of infants against HiB and tetanus toxin, based on antibody titers measured when infants were at least 7 months old, does not appear to be affected by in utero exposure to biologic therapy.

Section snippets

Study Cohort

The population for this study consisted of women enrolled in the Crohn’s and Colitis Foundation PIANO registry, an ongoing prospective multicenter registry initiated in 2007. This prospective registry approached women with an established diagnosis of IBD receiving care at 1 of 30 centers throughout the United States. Upon obtaining informed consent, women provided detailed information regarding their demographics and characteristics of their IBD, including current and past treatments.

Results

The study population included 179 women from the PIANO registry who completed the vaccination survey. The mothers’ mean age was 31.6 years and the mean disease duration at the time of pregnancy was 9.5 years (Table 1). Two-thirds (67%) had Crohn’s disease (n = 120). One third of women each were in their first (n = 67; 37%) or second pregnancy (n = 55; 31%), while 24 women (13.4%) were in their fourth or subsequent pregnancy. Most women had inactive (77%) or mild disease activity (18%) at the

Discussion

The impact of medications used for the management of maternal IBD on the health and development of infants historically has not been studied systematically. With data showing that in utero exposure to some biologics leads to persistence of drug concentrations for up to a year, there is a need for robust examination of this effect on infant immune response. By using data from a rigorously followed up prospective cohort of pregnant women with IBD, we show that the rates of adequate serologic

Acknowledgments

The authors acknowledge the valuable contributions of the participants and the research staff of the Crohn’s and Colitis Foundation Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes registry.

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    Conflicts of interest These authors disclose the following: Ashwin Ananthakrishnan has served on scientific advisory boards for Abbvie, Takeda, and Merck; Dawn Beaulieu has served as a consultant for Abbvie; Russell Cohen has served on the speaker’s Bureau for Abbvie and Takeda, has served as a consultant/on the advisory board/on the scientific advisory board for Abbvie, Celgene, Entera Health, Hospira, Janssen (Johnson & Johnson), Pfizer, Sandoz Biopharmaceuticals, Takeda, and UCB Pharma, has been the principal investigator for clinical trials for Astra-Zeneca, Celgene, Gilead Sciences, Medimmune, Mesoblast Ltd, Osiris Therapeutics, Pfizer, Receptos, RedHill Biopharma, Sanofi-Aventis, and UCB Pharma; Sunanda Kane has served as a consultant for Abbvie, Janssen, Samsung Bioepis, 11 Health, and Spherix Global Health, has received research funding from UCB, and has served on the GI Specialty Board for ABIM; and Uma Mahadevan has served as a consultant for Abbvie, Janssen, UCB, and Takeda. The remaining author discloses no conflicts.

    Funding This work was supported by the Crohn’s and Colitis Foundation.

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