By Will Boggs MD
NEW YORK (Reuters Health) - 19/6/2019
Anti-tumor necrosis factor (TNF) therapy in pregnant women with inflammatory bowel disease (IBD) can be discontinued before week 30 of gestation without increasing relapse risk or harming the fetus, researchers report.
"Data regarding risk of relapse in patients who stop anti-TNF during pregnancy is very sparse and conflicting," Dr. Mette Julsgaard from Aarhus University Hospital in Denmark told Reuters Health by email. "It is of great importance that we - in this largest prospective study to date - have established that discontinuation prior to gestational week 30 can safely be done without increased risk of relapse in the third trimester in women who have been in remission during 1st and 2nd trimester."
The American Gastroenterological Association recommends anti-TNF treatment throughout pregnancy or third-trimester dosing in women with IBD, whereas guidelines from the European Crohn's and Colitis Organization recommend stopping infliximab and adalimumab in the middle of the second trimester for women in remission to minimize fetal exposure.
Dr. Julsgaard and colleagues assessed relapse risk before delivery in women who discontinued anti-TNF treatment before gestational week 30, predictors of reduced infant birth weight and rates and satisfaction with counseling in their study of 153 pregnant women with IBD.
Among 120 women in remission during the first and second trimesters, relapse rates did not differ significantly between women who stopped anti-TNF treatment before gestational week 30 (1/46, 2%) and those who continued treatment (8/74, 11%; P=0.08), the researchers report in Inflammatory Bowel Diseases, online May 29.
The rates of preterm delivery, small for gestational age, low birth weight (<2,500 g), Apgar <7 and congenital malformations were low and did not differ significantly between infants in the two groups.
The median infant birth weight was significantly lower in those born to mothers who continued anti-TNF treatment beyond gestational week 30 (3,282 g) than in those born to mothers who discontinued anti-TIF treatment before gestational week 30 (3,505 g, P=0.0005). Results were similar in a subgroup analysis that included only women in self-reported remission throughout pregnancy.
Most women (88%) received counseling regarding treatment with biological therapy during pregnancy, and most expressed satisfaction with the information obtained, regardless of their risk of relapse.
Among all women, 88% said they would accept biological therapy during a future pregnancy. Among the 18 women who would not accept biological therapy or who weren't sure, 10 said they would have to balance the risks of both the biological treatment and a disease flare to their unborn child, and three had decided not to have more children for personal reasons unrelated to biological therapy.
"Anti-TNF treatment during pregnancy seems safe in the short term," Dr. Julsgaard said. "However, we only have very few studies investigating child development, risk of infections, and malignant diseases 4-5 years after exposure in utero. No long-term safety studies have been published. Minimizing (the effect of) neonatal exposure to anti-TNF on the development of the infants' immune system and increasing the likelihood of a higher infant birth weight by discontinuation of maternal treatment prior to gestational week 30 is the best care for pregnant patients in remission."
"Individualized counselling of pregnant patients is of great importance," she added. "The decision of whether to continue anti-TNF therapy in pregnancy should be a joint clinician and patient choice mainly determined by the risk of relapse in an individual woman."
Dr. Ligia Sassaki from Faculdade de Medicina de Botucatu, in Spain, who recently reviewed the safety of anti-TNF therapy in Crohn's disease during pregnancy and breast-feeding, told Reuters Health by email, "Previous studies have suggested that the presence of disease activity was the most important factor associated with negative outcomes, including low birth weight. In view of these findings, we must recognize that we don't know the real impact of anti-TNF drug exposure for fetal growth, and future studies are necessary."
"Physicians should know that the control of the disease is the key point to achieve better outcomes," said Dr. Sassaki, who was not involved in the study. "Anti-TNF drugs are safe during pregnancy, and patients should be instructed not to stop treatment without medical advice. Further studies are necessary to investigate the influence of drug exposure for fetal growth and development."
Dr. Julsgaard and several coauthors reported financial ties to manufacturers of anti-TNF agents.
Inflamm Bowel Dis 2019.