In the JournalsPerspective

TNF inhibitor use during pregnancy not linked to infection risk in offspring

Children born to mothers treated with TNF inhibitors for rheumatoid arthritis did not demonstrate an increased risk for infection, compared with both unexposed offspring and the general population, according to findings published in Arthritis & Rheumatology.

“Since animal studies did not show fetal risk, TNF [inhibitors] have been commonly and increasingly used during pregnancy, now prescribed in 20% of RA pregnancies, representing a 3-fold increase over the past 10 years,” Évelyne Vinet, MD, PhD, of McGill University Health Center, Montreal, and colleagues wrote. “Despite existing concerns that these potent drugs may cause immunosuppression, there are limited data on the risk of serious infection in exposed offspring.”

To determine the risk for serious infections among children born to mothers with RA who were exposed to TNF inhibitors during pregnancy, compared with those who were not exposed and the general population, the researchers analyzed U.S. claims information from the nationwide MarketScan commercial databases from 2011 to 2015. The researchers assembled a population-based cohort of 2,989 children of mothers with RA, 380 of whom were exposed to a TNF inhibitor, as well as a randomly selected control group of 14,596 children from the general population, whose mothers did not have RA.

Children born to mothers treated with TNF inhibitors for rheumatoid arthritis did not demonstrate an increased risk for infection, compared with both unexposed offspring and the general population, according to researchers.
Source: Shutterstock

Vinet and colleagues defined an infection as serious if it resulted in one or more hospitalizations, with infection as the primary diagnosis, during the first 12 months of life. In addition, they completed multivariate analyses, adjusting for maternal demographics, comorbidities, pregnancy complications and drugs.

According to the researchers, 3.2% of the children who were exposed to TNF inhibitors during gestation experienced serious infections (95% CI, 2-6.8), compared with 2% for unexposed children of mothers with RA (95% CI, 1.5-2.8) and 1.9% for those in the general population (95% CI, 1.9-2.5). After completing multivariate analyses, the researchers reported they were unable to determine an increased risk for serious infection among RA children exposed to TNF inhibitors, compared to unexposed RA offspring (OR = 1.4; 95% CI, 0.7-2.8) and non-RA children in the general population (OR = 1.7; 95% CI, 0.8-3.7).

However, the researchers also analyzed the risk for serious infections among RA children who had been exposed to infliximab (Remicade, Janssen), compared with other TNF inhibitors, and found a trend for an increased risk (OR = 3; 95% CI, 0.7-11.8). Still, the researchers noted that the CI included the possibility that there was no difference in relative risk.

“Within the largest cohort of RA offspring exposed to TNF [inhibitors] ever assembled, we did not detect a marked excess risk associated with over-all TNF [inhibitor] exposure during the preconception and gestational period,” Vinet and colleagues wrote. “However, we cannot exclude a differential risk according to specific TNF [inhibitors], with infliximab potentially resulting in a 3-fold increase in the risk of serious infections compared to other TNF [inhibitors]. More studies are needed to further evaluate if the risk of serious infections in exposed offspring is influenced by individual TNF [inhibitor] characteristics.” – by Jason Laday

Disclosure: Vinet reports support from a Fonds de Recherche du Québec Santé Clinical Research Scholar-Junior 1 Award. Please see the study for all other authors’ relevant financial disclosures.

Children born to mothers treated with TNF inhibitors for rheumatoid arthritis did not demonstrate an increased risk for infection, compared with both unexposed offspring and the general population, according to findings published in Arthritis & Rheumatology.

“Since animal studies did not show fetal risk, TNF [inhibitors] have been commonly and increasingly used during pregnancy, now prescribed in 20% of RA pregnancies, representing a 3-fold increase over the past 10 years,” Évelyne Vinet, MD, PhD, of McGill University Health Center, Montreal, and colleagues wrote. “Despite existing concerns that these potent drugs may cause immunosuppression, there are limited data on the risk of serious infection in exposed offspring.”

To determine the risk for serious infections among children born to mothers with RA who were exposed to TNF inhibitors during pregnancy, compared with those who were not exposed and the general population, the researchers analyzed U.S. claims information from the nationwide MarketScan commercial databases from 2011 to 2015. The researchers assembled a population-based cohort of 2,989 children of mothers with RA, 380 of whom were exposed to a TNF inhibitor, as well as a randomly selected control group of 14,596 children from the general population, whose mothers did not have RA.

Children born to mothers treated with TNF inhibitors for rheumatoid arthritis did not demonstrate an increased risk for infection, compared with both unexposed offspring and the general population, according to researchers.
Source: Shutterstock

Vinet and colleagues defined an infection as serious if it resulted in one or more hospitalizations, with infection as the primary diagnosis, during the first 12 months of life. In addition, they completed multivariate analyses, adjusting for maternal demographics, comorbidities, pregnancy complications and drugs.

According to the researchers, 3.2% of the children who were exposed to TNF inhibitors during gestation experienced serious infections (95% CI, 2-6.8), compared with 2% for unexposed children of mothers with RA (95% CI, 1.5-2.8) and 1.9% for those in the general population (95% CI, 1.9-2.5). After completing multivariate analyses, the researchers reported they were unable to determine an increased risk for serious infection among RA children exposed to TNF inhibitors, compared to unexposed RA offspring (OR = 1.4; 95% CI, 0.7-2.8) and non-RA children in the general population (OR = 1.7; 95% CI, 0.8-3.7).

However, the researchers also analyzed the risk for serious infections among RA children who had been exposed to infliximab (Remicade, Janssen), compared with other TNF inhibitors, and found a trend for an increased risk (OR = 3; 95% CI, 0.7-11.8). Still, the researchers noted that the CI included the possibility that there was no difference in relative risk.

“Within the largest cohort of RA offspring exposed to TNF [inhibitors] ever assembled, we did not detect a marked excess risk associated with over-all TNF [inhibitor] exposure during the preconception and gestational period,” Vinet and colleagues wrote. “However, we cannot exclude a differential risk according to specific TNF [inhibitors], with infliximab potentially resulting in a 3-fold increase in the risk of serious infections compared to other TNF [inhibitors]. More studies are needed to further evaluate if the risk of serious infections in exposed offspring is influenced by individual TNF [inhibitor] characteristics.” – by Jason Laday

Disclosure: Vinet reports support from a Fonds de Recherche du Québec Santé Clinical Research Scholar-Junior 1 Award. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Monica Richey

    Monica Richey

    The use of TNF inhibitor medication in pregnant women has always being of serious concern for all clinicians involved in their care. More data than ever is now available that is helping ease our minds.

    The article by Vinet and colleagues has shown for the first time that the rate of infections in children born to mother taking anti-TNFs during pregnancy — particularly in their third trimester — is relatively safe.

    The article brought to light very important information regarding the use of TNF inhibitors during pregnancy, including:

    • Not all TNF inhibitors are created equal; infliximab and adalimumab have the highest trans-placental transfer (reaching cord blood median levels at respectively 160% and 150% of maternal blood levels), while etanercept and certolizumab display the lowest passage (cord blood median levels at respectively 4-7% and less than 0.25% of maternal blood levels);
    • Mothers with RA had more pregestational diabetes (6.8%) and experienced more pregnancy complications, such as preterm births (11.8%) and gestational diabetes (21.6%), compared with the general population. In utero drug exposures to corticosteroids and non-biologic DMARDs were more frequent in RA offspring compared with offspring of non-RA mothers;
    • There was a trend for an increased risk of serious infections in RA offspring exposed to infliximab;
    • Over the first year of life, the percentage of serious infections in RA offspring with no TNF inhibitor exposure was almost identical (2.0%, 95% CI 1.5, 2.6) to non-RA offspring (1.9%, 95% CI 1.7, 2.2), while the percentage of serious infections in RA offspring with TNF inhibitor exposure was 3.2% (95% CI 1.5, 5.6).
    • The most frequent type of serious infections in RA offspring exposed to TNF inhibitors, unexposed RA offspring, and non-RA offspring was acute bronchiolitis due to respiratory syncytial virus, accounting for 36% (95% CI 14, 64), 31% (95% CI 19, 46), and 33% (95% CI 27, 38). No tuberculosis cases were identified.

    This is an incredibly important study, which not only highlights the safety of TNF inhibitors among the children of RA mothers but can also help us guide our patients and their families, through successful, painless and safe pregnancy, delivery and postpartum care of their children.

    • Monica Richey, MSN, ANP-BC/GNP
    • Board member, Rheumatology Nurses Society
      Nurse practitioner
      Division of rheumatology
      Northwell Health

    Disclosures: Richey reports no relevant financial disclosures.