Prenatal TNF inhibitor exposure not linked to serious infections

May 25, 2018

By Anne Harding

NEW YORK (Reuters Health) - Children of women with rheumatoid arthritis (RA) who are exposed to tumor necrosis factor-alpha inhibitors (TNFis) in the womb are not at markedly increased risk of serious infections, new findings suggest.

"It's reassuring for mothers who need to take these medications during pregnancy," Dr. Evelyne Vinet of McGill University Health Center in Montreal, Canada, told Reuters Health by phone. Nevertheless, she added, physicians caring for pregnant RA patients should continue to follow best-practice guidelines on discontinuing certain TNFis well before delivery.

Twenty percent of pregnant women with RA are prescribed TNFi medications, Dr. Vinet and her colleagues note in Arthritis & Rheumatology, online May 17. Animal studies have suggested that fetal exposure to the drugs is safe, they add, but most of these medications do cross the placenta.

Cord blood levels of infliximab and adalimumab can be well over maternal blood levels (160% and 150%, respectively), while passage to the fetus is lowest for etanercept and certolizumab, with median cord blood levels of 4% to 7% and less than 0.25%, respectively, in cord blood compared to maternal levels.

In the wake of a 2010 case report of an infant exposed to infliximab prenatally who died of disseminated tuberculosis after receiving a Bacillus Calmette-Guerin vaccine, concerns were raised that TNFi exposure could lead to immunosuppression, the researchers note. Based on these concerns, the European League Against Rheumatism recommends infliximab and adalimumab be stopped before 20 weeks' gestation and etanercept before 31-32 weeks, while certolizumab can be taken throughout pregnancy.

The researchers used 2011-2015 U.S. claim data on patients with commercial insurance through an employer to compare 2,989 RA offspring to 14,596 controls. In the RA group, 12.7% were exposed to TNFi prenatally, 4.5% were exposed during preconception, and 82.8% were not exposed.

Serious infections developed in 2% of offspring in the RA group during their first year of life, while 1.9% of offspring in the non-RA group had serious infections.

TNFi-exposed children had a 3.2% risk of serious infection. The risk was 3.2% for those exposed in the third trimester, and 1.5% for those exposed before conception.

Multivariate analyses did not indicate an increased risk of serious infections in TNFi-exposed children compared with the controls, or for preconception exposure.

"The OR estimates for serious infections in RA offspring exposed to TNFi during pregnancy versus unexposed RA offspring were fairly wide and precluded a definitive conclusion, (OR 1.4, 95% CI 0.7, 2.8), as were the results when we restricted TNFi exposure to the third trimester versus unexposed offspring," the authors state.

Offspring exposed to infliximab showed a trend toward increased risk of serious infections compared to infants exposed to other TNFi agents.

Acute bronchiolitis due to respiratory syncytial virus was the most common serious infection in all three groups, accounting for about one-third of all serious infections in each group. There were no cases of tuberculosis in exposed or unexposed RA offspring.

While the findings could not confirm an increased risk of TNFi drugs overall, Dr. Vinet noted, "we could not exclude a differential risk according to specific TNFi characteristics, with infliximab potentially resulting in a 3-fold increase in the risk of serious infections compared with other TNFis."


Arthritis Rheum 2018.

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