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Infants Exposed to Tofacitinib In Utero Experience Very Few Serious Infections, Study Says


The results will inform will inform counseling and management of pregnant women with inflammatory diseases who need tofacitinib or non-tumor necrosis factor inhibitors during pregnancy, said the author.

Very few serious infections were seen in children born to mothers with chronic inflammatory diseases who used biologics that are non-tumor necrosis factor inhibitor (non-TNFI) biologics or tofacitinib, an oral, small-molecule Janus kinase (JAK) inhibitor, compared with children not exposed to these drugs as well as children exposed to anti—tumor necrosis factors (anti-TNFs) in utero, according to an abstract presented at the American College of Rheumatology (ACR)’s 2019 meeting, being held in Atlanta, Georgia, this week.

Tofacitinib was first approved in 2012 to treat adult patients with rheumatoid arthritis who did not respond well to methotrexate. In 2017, it was cleared for patients with psoriatic arthritis who did not respond well to methotrexate or other similar medicines, and it was approved for ulcerative colitis, part of inflammatory bowel conditions (IBD), in 2018.

Non-TNF biologics include abatacept, rituximab, and tocilizumab. Anti-TNF biologics include etanercept, infliximab, and adalimumab.

The study identified all women with 1 or more hospitalization for delivery after a diagnosis of RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), psoriasis, or inflammatory bowel diseases (IBD), and a randomly selected group of unaffected mothers, matched 4:1 for age, year of delivery, and state of residence. Researchers used the MarketScan database for the period 2011 to 2016.

The researchers defined drug exposure as 1 or more filled prescription and/or infusion procedure codes during pregnancy and/or the preconception period. The anti-TNF biologics included in the study were abatacept, rituximab, tocilizumab, ustekinumab and vedolizumab.

Serious infections in the offspring were defined as 1 or more hospitalizations with infection as the primary diagnosis within the first year of life.

Exposure groups in the study were characterized by maternal demographics, disease type, comorbidities, pregnancy complications and use of drugs, such as corticosteroids, non-biologic disease modifying agents, or biologics.

Participants included 16,490 offspring of mothers with RA (4142), AS (381), psoriasis or PsA (5743) and IBD (6731), as well as 164,553 children born to unaffected matched mothers.

Among the offspring of mothers who had inflammatory diseases, 105 were exposed to tofacitinib or non-TNFi biologics, including 4 to tofacitinib, 33 to abatacept, 4 to rituximab, 12 to tocilizumab, 42 to ustekinumab and 10 to vedolizumab. In addition, 1611 offspring were exposed to anti-TNF biologics during pregnancy.

The researchers found 2 cases of serious infections in children exposed to tofacitinib or non-TNFi biologics: 1 to tofacitinib and 1 to abatacept.

They found that the percent of serious infections in offspring of inflammatory disease mothers with no anti-TNF exposure was 2.1, while for those with exposure in utero exposure, it was 2.3. They also found 1.6% of children born to unaffected mothers had serious infections.

Pregnant patients are excluded from clinical trials, noted Evelyne Vinet, MD, PhD, associate professor of rheumatology and clinical epidemiology at McGill University in Montreal, Canada, and the study’s lead author, and real-world evidence is lacking. Moreover, some women find that their disease worsens in pregnancy and may negatively impact pregnancy outcomes.

During pregnancy, circulating immunoglobulin G (IgG) antibodies from the mother are actively transported across the placenta. Some biologic drugs have the potential to cross the placenta too, and often reach higher levels in the fetus than in the mother. This possibility raises concerns that exposed offspring could develop immunosuppression.

In addition, it has also been hypothesized that small-molecule drugs may cross the placenta, although this remains unconfirmed.

“Our findings will help guide counseling and management of pregnant women with inflammatory arthritis that require non-TNFi biologics and tofacitinib during pregnancy,” she said.


Vinet E, St-Pierre Y, Moura CS, Curtis J, Bernatsky S. Serious infections in offspring exposed in utero to non-TNFi biologics and tofacitinib. Presented at: The American College of Rheumatology Annual Meeting, November 8-13, 2019; Atlanta, Georgia.

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