Nav: Home

Babies exposed to TNFi or tofacitinib in utero experience very few serious infections

November 09, 2019

ATLANTA -- A new study found that very few serious infections were seen in children born to mothers with chronic inflammatory diseases who used non-TNFi biologics or tofacitinib during pregnancy compared to children not exposed to these drugs and children exposed to TNFi biologics in utero. These findings are being presented this week at the 2019 ACR/ARP Annual Meeting (Abstract #1901).

Treatments for some rheumatic diseases may include tumor necrosis factor inhibitors (TNFi) or tofacitinib. TNFi is a group of medications used worldwide to treat inflammatory conditions that reduces inflammation and can stop disease progression by targeting an inflammation-causing substance called tumor necrosis factor. Tofacitinib is an oral, small molecule drug used to treat adults with moderately to severely active rheumatoid arthritis (RA) in which methotrexate did not work well.

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 (a partial or complete suppression of the immune response of an individual). This large cohort study compared 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.

"Our overarching goal is to provide pregnancy safety data on new biologic and small molecule drugs used to treat women with inflammatory arthritis. These conditions predominantly affect women, particularly during their childbearing years. In pregnant women with inflammatory arthritis, flares are common and associated with adverse pregnancy outcomes. Disease control with effective drugs is often warranted," says Evelyne Vinet, MD, PhD, Associate Professor of Rheumatology and Clinical Epidemiology at McGill University in Montreal, Canada, and the study's lead author. "Yet, data in pregnant women and their offspring is lacking, as pregnant patients are excluded from clinical trials. Our findings will help guide counseling and management of pregnant women with inflammatory arthritis that require non-TNFi biologics and tofacitinib during pregnancy."

The researchers identified women with one or more hospitalizations for delivery after a diagnosis of RA, ankylosing spondylitis (AS), psoriasis (PsO), psoriatic arthritis (PsA) or inflammatory bowel diseases (IBD). They also randomly selected a group of unaffected mothers, matched 4:1 for age, year of delivery and state of residence, using the MarketScan database from 2011 to 2016. Only women continuously enrolled in MarketScan for 12 months or longer prior to their deliveries and with available child linkage information were included in the study.

The researchers defined tofacitinib, TNFi and non-TNFi biologic exposure based on one or more filled prescription and/or infusion procedure codes during pregnancy and/or the preconception period. Non-TNFi drugs include abatacept, rituximab, tocilizumab, ustekinumab and vedolizumab. They defined serious infections in the offspring based on one or more hospitalizations with infection as the primary diagnosis within the first year of life. They also characterized all the exposure groups in the study according to maternal demographics, disease type, comorbidities, pregnancy complications and use of drugs, such as corticosteroids, DMARDs or biologics.

Participants included 16,490 offspring of mothers with RA (4,142), AS (381), PsO or PsA (5,743) and IBD (6,731), 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 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 pregnancy.

The researchers found two cases of serious infections in children exposed to tofacitinib or non-TNFi biologics: one to tofacitinib and one to abatacept. They found that the percent of serious infections in offspring of inflammatory disease mothers with no TNFi exposure was 2.1, while for those with TNFi in utero exposure, it was 2.3. They also found 1.6 percent of children born to unaffected mothers had serious infections.

Additional research is needed to determine the specific effects of individual non-TNFi biologics during pregnancy, as well as small molecule drugs for inflammatory diseases, the researchers concluded.

"Our project innovates by using 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," says Dr. Vinet. "We provide the first data on infectious risk in offspring exposed to non-TNFi biologics and tofacitinib. This is a first step, as we need more data to confirm safety, particularly regarding other pregnancy outcomes. It is imperative that we further study this issue to provide firm evidence to guide treatment decisions prior to conception and throughout pregnancy."
-end-
About the ACR/ARP Annual Meeting

The ACR/ARP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, it offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit https://www.rheumatology.org/Annual-Meeting, or join the conversation on Twitter by following the official #ACR19 hashtag.

About the American College of Rheumatology

The American College of Rheumatology (ACR) is an international medical society representing over 8,500 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases.

ABSTRACT

Serious Infections in Offspring Exposed in Utero to Non-TNFi Biologics and Tofacitinib

Background/Purpose: During pregnancy, maternal circulating immunoglobulins G (IgG) are actively transported across the placenta through their Fc portion. Thus, TNFi and other biologics harboring an Fc part have the potential to transfer across the placenta, often reaching higher fetal than maternal levels. In addition, it is postulated that small-molecule drugs may cross the placenta, although this remains unconfirmed. As fetuses could be exposed to therapeutic (or potentially supra-therapeutic) levels of biologics and small molecules, there are concerns that these agents could cause immunosuppression in exposed offspring. We compared the risk of serious infections in children born to mothers with chronic inflammatory diseases who used non-TNFi biologics or tofacitinib during pregnancy, versus unexposed offspring and children exposed to TNFi in utero.

Methods: We identified all women with ?1 hospitalization for delivery after a diagnosis of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis (PsO), psoriatic arthritis (PsA), 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, using MarketScan database (2011-2016). Only women continuously enrolled within MarketScan for ?12 months prior to delivery and with available child linkage were included. We defined tofacitinib, TNFi and non-TNFi biologic (i.e. abatacept, rituximab, tocilizumab, ustekinumab, vedolizumab) exposure based on ?1 filled prescription and/or infusion procedure code during pregnancy and/or the preconception period. We ascertained serious infections in the offspring based on ?1 hospitalization with infection as a primary diagnosis, within the first year of life. We also characterized all exposure groups according to maternal demographics, disease type, co-morbidities, pregnancy complications, and drug use (i.e. corticosteroids, DMARDs, biologics).

Results: We identified 16,490 offspring of mothers with RA (4,142), AS (381), PsO/PsA (5,743), and IBD (6,731), as well as 164,553 children born to unaffected matched mothers. Among offspring whose mothers had inflammatory diseases, 105 were exposed to tofacitinib or non-TNFi biologics (tofacitinib 4, abatacept 33, rituximab 4, tocilizumab 12, ustekinumab 42, vedolizumab 10) and 1,611 to TNFi during pregnancy. We observed 2 cases of serious infections in children exposed to tofacitinib or non-TNFi biologics (1.9%; 95% CI 0.3, 7.4): one case was exposed to tofacitinib, while the other was exposed to abatacept. The percent of serious infections in offspring of inflammatory disease mothers with no TNFi exposure was 2.1% (95% CI 1.9, 2.3), while for those with TNFi in utero exposure, it was 2.3% (95% CI 1.6, 3.0). In children born to unaffected mothers, the percent of serious infections was 1.6% (95% CI 1.6, 1.7).

Conclusions: In the largest cohort of inflammatory disease offspring ever assembled, we detected very few serious infections in children exposed to non-TNFi biologics or tofacitinib. More studies are necessary to precisely determine the specific effects of individual non-TNFi biologic and small-molecule drugs.

American College of Rheumatology

Related Pregnancy Articles:

Medication use during pregnancy is common in women with preeclampsia
Use of medications during pregnancy is more common in women with preeclampsia than in those without, according to a British Journal of Clinical Pharmacology analysis of women who gave birth at a hospital in Finland in 2002-2016.
Going to sleep on your back in late pregnancy
This study looked at whether going to sleep on your back in the third trimester of pregnancy was associated with average lower birth weights.
Opioid use disorder in pregnancy: 5 things to know
Opioid use is increasing in pregnancy as well as the general population.
Medical imaging rates during pregnancy
Researchers looked at rates of medical imaging (CT, MRI, conventional x-rays, angiography, fluoroscopy and nuclear medicine) during pregnancy in this observational study that included nearly 3.5 million pregnant women in the United States and Canada from 1996 to 2016.
New research on diet and supplements during pregnancy and beyond
The foods and nutrients a woman consumes while pregnant have important health implications for her and her baby.
Obesity in early pregnancy linked to pregnancy complications
In a prospective study published in Obesity of 18,481 pregnant women in China who had never given birth before, obesity in early pregnancy was linked to higher risks of spontaneous abortion, preterm birth, and large birth weight in newborns.
Possible link between autism and antidepressants use during pregnancy
An international team led by Duke-NUS Medical School has found a potential link between autistic-like behaviour in adult mice and exposure to a common antidepressant in the womb.
Immigrant women more likely to be overweight during pregnancy
A new study in the Journal of Public Health finds that women in Norway from immigrant backgrounds are more likely to be overweight during pregnancy.
Stillbirths more likely if diabetes in pregnancy not diagnosed
Women who develop diabetes in pregnancy but are not diagnosed are much more likely to experience stillbirth than women without the condition, according to new research.
Do economic conditions affect pregnancy outcomes?
Economic downturn during early pregnancy was linked with modest increases in preterm birth in a Paediatric and Perinatal Epidemiology analysis.
More Pregnancy News and Pregnancy Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Accessing Better Health
Essential health care is a right, not a privilege ... or is it? This hour, TED speakers explore how we can give everyone access to a healthier way of life, despite who you are or where you live. Guests include physician Raj Panjabi, former NYC health commissioner Mary Bassett, researcher Michael Hendryx, and neuroscientist Rachel Wurzman.
Now Playing: Science for the People

#544 Prosperity Without Growth
The societies we live in are organised around growth, objects, and driving forward a constantly expanding economy as benchmarks of success and prosperity. But this growing consumption at all costs is at odds with our understanding of what our planet can support. How do we lower the environmental impact of economic activity? How do we redefine success and prosperity separate from GDP, which politicians and governments have focused on for decades? We speak with ecological economist Tim Jackson, Professor of Sustainable Development at the University of Surrey, Director of the Centre for the Understanding of Sustainable Propserity, and author of...
Now Playing: Radiolab

An Announcement from Radiolab