Should Pregnant Patients With Inflammatory Diseases Use Anti-TNF Agents?

A recent retrospective review published in the International Journal of Molecular Sciences sought to evaluate the safety of anti—tumor necrosis factor (anti-TNF) therapy in pregnant women who had a broad range of chronic inflammatory diseases. Researchers identified meta-analyses, systematic reviews, narrative reviews, observational studies, and guidelines within their search of PubMed to include in the retrospective analysis.

One of the main concerns attributed to anti-TNF treatment during pregnancy is the ability for the therapy to be transferred to the fetus. Complete immunoglobulin G (IgG) antibodies, both maternal and therapeutic, are delivered to the placenta during pregnancy naturally. This fact is important for patients who are treated with adalimumab, golimumab, and infliximab, which are complete IgG1 anti-TNF antibodies, and therefore transferred easily to the placenta.

Adverse Maternal Outcomes

Adverse obstetric events during pregnancy include preeclampsia, essential thrombocythemia, gestational diabetes, hypertension, infections, venous thromboembolism, intensive care unit admission, and cesarean section.

In a retrospective multicenter study in pregnant women with inflammatory bowel disease (IBD), the rate of preeclampsia was similar in patients exposed to anti-TNF agents and non-exposed patients. To the knowledge of the researchers, no further studies have addressed adverse maternal outcomes in women exposed to anti-TNF drugs.

Women with IBD have an increased risk of adverse maternal and neonatal outcomes if their disease is active during pregnancy. The European Crohn’s and Colitis Organisation recommends that these women are best treated appropriately and promptly, and if the disease allows it, treatment with anti-TNF drugs should be discontinued around gestational week 24 to week 26.

Adverse Pregnancy Outcomes

Adverse pregnancy outcomes are defined as spontaneous abortion, elective termination, ectopic pregnancies, intrauterine death, and stillbirth. A meta-analysis in women treated with anti-TNF drugs for IBD found that the rate of elected terminations was 17% versus 0.02% in the background population. However, spontaneous abortions were 12% in the anti-TNF agent—exposed pregnancies compared with 20% in the background population. There were no ectopic pregnancies or stillbirths noted in the trial.

Adverse Fetal and Neonatal Outcomes

Adverse fetal and neonatal outcomes include congenital malformations, preterm birth, low birth weight (less than 2500g), small size for gestational age, intrauterine growth retardation, respiratory distress syndrome, neonatal infections, admission to neonatal intensive care unit, and death.

One recent systematic review found a trend towards anti-TNF drug—specific harm with increased risk of congenital malformations and preterm birth in infants of women with chronic inflammatory diseases other than psoriasis who were exposed to anti-TNF drugs. Conversely, a 2016 meta-analysis found no increased risk of congenital malformations in the exposed women with IBD versus disease-matched controls.

Through the review of prior studies, researchers found that most literature achieved a consensus that women with chronic inflammatory disease of any type during pregnancy should receive multidisciplinary care that incorporates a team with experience in handling women with active disease both during pregnancy and the postpartum period.

Reference

Johansen CB, Jimenez-Solem E, Haerskjold A, Sand FL, Thomsen SF. The use and safety of TNF inhibitors during pregnancy in women with psoriasis: a review. Int J Mol Sci. 2018;19(5):1349. doi: 10.3390/ijms19051349.