2017-12-20 06:07:26 UTC

Does Immunomodulator Therapy for IBD During Pregnancy Affect Newborn Response to Vaccines?

Rates of adequate serologic response to Haemophilus influenzae B (HiB) and tetanus vaccines are similar among infants born to women with inflammatory bowel diseases (IBD) treated with immunomodulator or biologic agents compared to women who did not receive these immunosuppressive drugs during pregnancy, researchers report in the January issue of Clinical Gastroenterology and Hepatology. There was also no association between cord blood or infant serum concentrations of biologics and adequacy of vaccine titers.

Proportion of infants with protective titers to HiB and tetanus vaccine, grouped by mothers’ use of biologic agents. A total of 46 (38 biologic exposed, 8 unexposed) and 49 (41 biologic exposed, 8 unexposed) infants had an available vaccine titer response to HiB and tetanus, respectively.

Many patients with IBDs such as Crohn’s disease and ulcerative colitis require immunosuppressive biologic therapies to control disease activity, which is important in women because active IBD has been associated with adverse pregnancy outcomes. Multiple retrospective studies have found no association between treatment of pregnant women with IBD using biologic agents such as antagnoists of tumor necrosis factor (anti-TNF) and adverse pregnancy outcomes.

However, some of these drugs can cross the placenta; anti-TNF agents such as adalimumab or infliximab can be detected in infants until 12 months of age. In contrast, certolizumab pegol, which is a polyethylene glycolylated FaB immunoglobulin, does not bind to the neonatal Fcγ receptor that mediates transplacental transfer and was not found in infant or cord blood.

There are limited data on the long-term effects of this exposure on the development of the neonatal immune system.

Dawn B. Beaulieu et al performed a large, prospective study to determine whether exposure of women to these agents during pregnancy affects serologic responses to vaccines in newborns.

They collected data from women in 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. Serum samples collected from infants at least 7 months old were analyzed for titers of antibodies to Haemophilus influenzae B (HiB) or tetanus toxin.

A total of 179 women completed a vaccine survey (26 biologic unexposed, 153 exposed to a biologic agent). Umbilical cord blood samples from 33 infants were assayed for concentration of biologic agents, and vaccination response was compared between infants born to mothers exposed to biologic therapy (infliximab, adalimumab, certolizumab, 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.

Beaulieu et al found no significant difference in proportions of infants with protective antibody titers against HiB born to drug-exposed mothers (n = 42, 71%) vs unexposed mothers (n = 8, 50%) (see figure). Similarly, 80% of infants exposed to biologic therapy had an adequate immune response to the vaccine for tetanus toxoid compared with 75% of unexposed infants.

There were no differences in proportions of infants with responses to vaccines among groups with undetectable levels of the drugs (50% had a response), therapeutic levels of the drugs (3–10 mcg/mL; 100% had a response), high levels of the drugs (10.1–20 mcg/mL; 83% had a response ), or very high levels of the drugs (>20 mcg/mL; 59% had a response).

The median concentration of infliximab in cord blood did not differ significantly between infants with vs without protective antibody titers to HiB or tetanus toxoid.

Because infliximab was the most commonly used biologic agent, Beaulieu et al performed a subgroup analysis of women receiving this therapy. The authors found no association between infliximab concentration in cord blood and adequacy of immune response to HiB or tetanus vaccines.

Infants born to 43 of the women on biologics (19 infliximab, 12 certolizumab, 7 adalimumab, and 1 infliximab, certolizumab, or ustekinumab) received the rotavirus vaccine. Among infants of 40 women for whom these data were available, 7 (17.5%) reported a reaction to the vaccine. Of these, 6 infants had a fever (5 infliximab, 1 adalimumab) and 1 had diarrhea (on infliximab). There was no correlation between infant drug concentration at birth and the likelihood of a reaction to the rotavirus vaccine. The authors state that these rates of reaction are comparable with the rates of fever (42%) or diarrhea (19%) reported for healthy infants in the general population.

Beaulieu et al conclude that the rates of adequate serologic response to HiB and tetanus vaccines are similar among infants born to women receiving biologic therapies for IBD compared with women with IBD who were not treated with these drugs during pregnancy. The authors found no association between cord blood or infant serum concentrations of biologics and adequacy of vaccine titers.

There have been several other studies of the effects of immunosuppression on response to vaccination in patients with IBD. A study in 2007 of 80 children (51 with IBD) who received inactivated influenza vaccines found that fewer children with IBD developed protective titers to 3 different influenza virus antigens than children without IBD, and reported a reduced serologic response in children receiving combination therapy.

Further studies are needed to assessed the serologic response to additional vaccines and over multiple timepoints.

 

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