Emerging data on the use of anti‐tumor necrosis factor‐alpha medications in pregnancy

Abstract

Anti-tumor necrosis factor (TNF) α medications are used for the treatment of a number of autoimmune diseases. Evaluation of pregnancy safety for these medications is complicated by the contribution of the underlying maternal disease to adverse pregnancy outcomes, such as preterm delivery and reduced birth weight. Placental transport of these medications is thought to be minimal in the first trimester, thereby providing some reassurance regarding theoretical risks for congenital malformations. Available human exposure data are sparse; however, to date there has been no convincing evidence to support an increased risk for a specific pattern of major congenital malformations with any of the drugs in this group for which some data is currently available. As a result of the improvement of symptoms during pregnancy in some women with autoimmune diseases, it may be possible to discontinue treatment before or shortly after conception. However, in some cases the benefits of treatment and concerns for disease flares in pregnancy have warranted continued treatment during pregnancy. Because of the relatively long half-life of these medications, and theoretical concerns for immune compromise of the infant following exposure in the latter two trimesters, some clinicians recommend discontinuation of treatment in the third trimester to avoid potentially prolonged infant exposure in the postpartum period. Currently ongoing controlled cohort studies for some of the TNF blocker medications will help to provide more definitive answers for clinicians and patients.

Update on biologic safety for patients with psoriasis during pregnancy

“…Immunoglobulin G (IgG) is the only major class of antibody that is transported across the human placenta. Fetal levels of IgG in umbilical venous blood are low in the first two trimesters of pregnancy and do not surpass maternal levels of IgG until the beginning of the third trimester when active transport of the IgG molecules across the placenta increases rapidly (Chambers and Johnson, 2012). Transport of IgG is facilitated by the neonatal Fc receptor (FcRn) on the placenta.…”

“…One case report of a death due to disseminated Bacillus Calmette-Guérin (BCG) infection following live BCG vaccination in an infant borne to a mother receiving infliximab during pregnancy, caused significant and warranted alarm (Cheent et al, 2010). Multiple studies have documented that levels of anti-TNF agents are detected in infants at birth and decline thereafter (Chambers and Johnson, 2012); however, a few studies noted that drug clearance could take up to 1 year after birth (Julsgaard et al, 2016). Infliximab clears more slowly than adalimumab (Julsgaard et al, 2016).…”

Inflammatory and glandular skin disease in pregnancy

“…57 The use of TNF-α inhibitors in pregnancy remains controversial, and biologic medications should only be used only if benefit greatly outweighs the risks and all other A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 16 treatment options have been exhausted. 76 Surgical therapy is considered as a last resort for cases of extensive or refractory disease.…”

Therapeutic options for the treatment of non-infectious uveitis

“…All the anti-TNF agents are currently classified as pregnancy category B (no fetal harm in animal studies, but inadequate studies in pregnant women). Numerous pregnancies inadvertently occurring while on these agents during the first trimester have been reported [104], and there has not been an increased risk of congenital malformations reported with the use of either infliximab or adalimumab during pregnancy [105]. Also, case reports have shown that children who were breastfed during maternal treatment with TNF inhibitors had normal growth and development [106].…”