Few Serious Infections in Babies Exposed to Non-TNF-inhibitor Biologics or Tofacitinib

By Megan Brooks

November 19, 2019

NEW YORK (Reuters Health) - Children born to mothers with chronic inflammatory diseases who took non-tumor-necrosis-factor inhibitor (TNFi) biologics or tofacitinib while pregnant appear to be at low risk of developing serious infections, a new analysis suggests.

"Our findings help to address the important knowledge gap in biologic and small-molecule drug safety in pregnancy and our data are reassuring as we detected very few serious infections in exposed offspring," Dr. Evelyne Vinet of McGill University in Montreal, Canada, told Reuters Health by email. "In addition, the risk of serious infection was similar to the risk observed in TNFi exposed offspring as well as in unexposed offspring."

Dr. Vinet reported the results November 9 in Atlanta during the American College of Rheumatology annual meeting.

During pregnancy, circulating immunoglobulin G (IgG) antibodies from the mother cross the placenta. Some biologic agents also have the potential to cross the placenta, and may reach higher levels in the fetus than in the mother, raising concerns that exposed offspring could develop immunosuppression.

Yet, data in pregnant women and their offspring is lacking because pregnant women are excluded from clinical trials, Dr. Vinet and colleagues note in their meeting abstract.

In a large cohort study, they compared the risk of serious infections in children born to mothers with chronic inflammatory diseases who took non-TNFi biologics or tofacitinib during pregnancy with unexposed children and children exposed to TNFi biologics in utero.

Participants included 16,490 offspring of mothers with either rheumatoid arthritis (n=4,141), ankylosing spondylitis (381), psoriatic osteoarthritis or psoriatic arthritis (5,743) or inflammatory bowel disease (6,731) receiving non-TNFi biologics or tofacitinib while pregnant and 164,553 children born to unaffected matched mothers.

In terms of exposure, 105 children were exposed to tofacitinib or non-TNFi biologics, including four to tofacitinib, 33 to abatacept, four to rituximab, 12 to tocilizumab, 42 to ustekinumab and 10 to vedolizumab. In addition, 1,611 offspring were exposed to TNFi biologics during gestation.

The researchers defined serious infections as one or more hospitalization with infection as a primary diagnosis within the first year of life.

They found only two cases of serious infections in children exposed to tofacitinib or non-TNFi biologics (1.9%) - one to tofacitinib and one to abatacept.

The percentage of serious infections among children born to mothers with inflammatory diseases with no exposure to TNFi was 2.1%, compared with a rate was 2.3% for those with TNFi exposure in utero. In addition, 1.6% of children born to unaffected mothers had a serious infection in the first year of life.

This study represents "the largest cohort of pregnant women with chronic inflammatory diseases ever assembled to address drug safety in pregnant women, who are regularly excluded from clinical trials. We provide the first data on infectious risk in offspring exposed to non-TNFi biologics and tofacitinib," Dr. Vinet said in a conference statement.

"More studies are needed to precisely determine the risk of serious infections associated with each individual non-TNFi biologic and small-molecule drug, as the number of exposed offspring for each specific agent was limited," she added in her email to Reuters Health.

SOURCE: http://bit.ly/2K8DMtp

American College of Rheumatology 2019.