Continuing anti-tumor necrosis factor (anti-TNF) therapy after 24 weeks of pregnancy is associated with a lower likelihood of relapse of inflammatory bowel disease (IBD) in pregnant women and fewer premature deliveries, according to a new report.
In addition, the numbers of Cesarean sections, stillbirths, serious infections, and small or large weight for gestational size were similar in patients who continued or discontinued anti-TNF treatment after 24 weeks.
"Discontinuation of anti-TNF treatment was associated with increased IBD activity and consequently with an increased rate of preterm birth," lead author Antoine Meyer, MD, PhD, a gastroenterologist at Assistance Publique-Hopitaux de Paris, France, and colleagues conclude.
"These results provide strong evidence supporting the recommendation of maintaining anti-TNF throughout pregnancy in women with IBD," they write.
The study was published online September 26 in the Annals of Internal Medicine.
Analyzing IBD During Pregnancy
About 3.3 million people in North America and 3.2 million people in Europe live with Crohn's disease or ulcerative colitis, which often affects young women during their childbearing years, the study authors write. North American guidelines recommend the continuation of anti-TNF therapy throughout pregnancy, whereas European guidelines advise to consider stopping anti-TNF treatment around 24 weeks; therefore, researchers are conducting large studies to understand any differences in maternal, pregnancy, and infant outcomes during the third trimester.
In this study, Meyer and colleagues analyzed data from the French national health data system, called the Systeme National des Donnees de Sante, to emulate a target trial evaluating the benefits and risks of anti-TNF continuation after 24 weeks of pregnancy between 2010 and 2020.
The research team looked for maternal IBD relapse up to 6 months after pregnancy, adverse pregnancy outcomes, and serious infections in babies during the first 5 years of life. To mimic randomization, they used inverse probability weighting to reduce confounding.
Among the 184,115 women with IBD, 68,209 pregnancies ended between April 2010 and December 2020. Of those, 5413 pregnancies reached 24 weeks and were exposed to anti-TNF therapy before 24 weeks. Among those pregnancies, anti-TNF treatment was stopped in 2890 (54.6%) and continued in 2403 (45.4%) after 24 weeks.
At baseline, there were no major differences between the two groups. Few patients had comorbidities, such as diabetes, obesity, or antihypertensive therapy. Among those who took an anti-TNF during pregnancy, 50% took infliximab, 47.2% took adalimumab, 2.5% took golimumab, and 1.3% took certolizumab.
Overall, prescription of anti-TNF therapy during pregnancy after 24 weeks was associated with less IBD relapse between 32 weeks of pregnancy and 6 months after delivery, at 35.8% versus 39%. In the 6 months after delivery, 88.3% of women who continued anti-TNF after 24 weeks were still treated with anti-TNF, while 71.1% of those who had stopped anti-TNF had restarted it.
Regarding pregnancy outcomes, continuing anti-TNF after 24 weeks was associated with a lower rate of prematurity, at 7.6% versus 8.9%. There was little difference in the frequency of pregnancy-related hospitalizations after 32 weeks, Cesarean sections, stillbirths, and small and large for gestational age at birth.
Among 5135 children born from 5047 pregnancies and 4172 mothers with IBD, there were 1013 serious infections during the first 5 years of life. The overall rate of serious infection was similar for both groups, with 54.2 per 1000 person-years among those who continued anti-TNF and 50.2 per 1000 person-years among those who stopped anti-TNF. Similar rates continued through the first 5 years of life, regardless of the year of life.
Children who were exposed to anti-TNF after 24 weeks had a higher rate of ear, nose, and throat infections. However, there was no difference in the rates of infections of other sites or of bacterial, viral, or opportunistic infections.
Pregnancy outcomes were similar for patients with Crohn's disease versus ulcerative colitis, as well as those exposed to intravenous versus subcutaneous anti-TNF.
"Healthy mother equals healthy baby. It is very important that women with IBD see their gastroenterologist and OB [obstetrician] prior to attempting conception to ensure they are in remission and have a medication plan," Uma Mahadevan, MD, professor of medicine and director of the Colitis and Crohn's Disease Center at the University of California, San Francisco, told Medscape Medical News.
Mahadevan, who wasn't involved with this study, has researched biologic therapies, such as anti-TNF, during pregnancy as part of the Pregnancy in IBD and Neonatal Outcomes (PIANO) study. Mahadevan and colleagues have recommended continuation of therapy throughout pregnancy.
"This large French study is very reassuring that continuing anti-TNF during pregnancy is not harmful to mother or infant, and stopping is associated with adverse events to mother and infant," she said. "This confirmation on a large scale of existing data is important for the management of this vulnerable population."
The study authors note the limitation of using algorithms rather than clinical data to identify patients with IBD, pregnancies, and serious infections. At the same time, the comprehensive database and specific criteria used in the study likely captured the relevant data accurately, they say.
"This study was large enough to detect small differences and rare outcomes, such as stillbirths or serious infection sites," the study authors write. "All patients were treated within the setting of the French national health system, which provides equal access to healthcare to French residents."
Now researchers are looking at other biologics during pregnancy. These therapies include new biologics, such as ustekinumab, vedolizumab, and risankizumab, as well as small molecule inhibitors, such as tofacitinib and upadacitinib.
In addition, research teams are studying whether men with IBD experience negative fertility or reproductive outcomes after anti-TNF exposure.
"We recently examined this topic and also found reassuring data that paternal exposure to anti-TNF biologics does not impair semen parameters/male fertility or increase the risk of adverse pregnancy outcomes," John Mark Gubatan, MD, instructor of medicine at Stanford University, California, told Medscape Medical News.
Gubatan, who wasn't involved with this study, also published recent research that found continuation of anti-TNF biologics during the third trimester wasn't associated with adverse pregnancy outcomes or serious infant infections.
"Data to quantify the risks and benefits of stopping or continuing anti-TNF biologics are crucial to inform clinical management," he said. "Some clinicians and patients have opted to delay or stop anti-TNF biologics during the third trimester. However, this strategy also may increase the risk of IBD flares and relapse."
The study was initiated by the French National Health Service and did not receive funding from any private entities. The authors, Mahadevan, and Gubatan have reported no relevant financial relationships.
Ann Intern Med. Published online September 26, 2022. Abstract
Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.
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Cite this: Using Anti-TNF Therapy After 24 Weeks of Pregnancy Appears Safe, Effective: Study - Medscape - Sep 26, 2022.