Are biological drugs safe in pregnancy?

Abstract

The introduction of biological therapies has significantly improved the outcome of inflammatory rheumatic diseases. As most of these diseases affect women and men in childbearing age, some concerns have been voiced as to the safety of these drugs in relation to reproduction and pregnancy. Data from many hundreds of pregnancies in patients affected by inflammatory bowel disease and inflammatory arthritis have suggested that exposure to anti-TNF therapies at conception and/or during pregnancy is not associated with adverse pregnancy outcomes or any increase in congenital abnormalities. However, the exposure to anti-TNFα agents, particularly to monoclonal antibodies, in late pregnancy is associated with high drug levels in the newborn and their long-term effects on children remain unknown. Therefore, limiting the use of anti-TNFα to the first 30 weeks of pregnancy is recommended to reduce fetal exposure. Live-virus vaccines should be given only when levels of anti-TNFα drugs are undetectable in the serum of infants. Studies suggest that many of these drugs do enter breast milk in small amounts, but the extent to which the infant absorbs them is less clear. Limited reports have not suggested adverse pregnancy outcomes in women whose partners were exposed to anti-TNF therapies at the time of conception. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab and belimumab are limited and their use in pregnancy cannot currently be recommended.

Pregnancy in Takayasu Arteritis Patients Exposed to Anti-Tumour Necrosis Factor (Anti-TNF)-α Therapy

“…7 Live vaccines are recommended after 6 months of age in infants exposed to anti-TNF in utero. 8 To the best of our knowledge, this is the first report describing the use of anti-TNF agents in pregnant TA patients.…”

Impfungen bei Immundefekten/Immunsuppression – Expertenstatement und Empfehlungen

“…Darü-ber hinaus wird dieses Risiko durch die zur Behandlung eingesetzten immunsuppressiven Medikation erhöht [85]. [112].…”

“…Lebendimpfungen bei Kindern, die in utero Biologika-exponiert waren, dürfen in den ersten 6 Monaten nicht gegeben werden bzw. sollen erst dann gegeben werden, wenn kein Biologikum mehr im Blut nachweisbar ist [112].…”

“…Daten zur Gabe von Rituximab, Abatacept, Anakinra, Tocilizumab und Belimumab in der Schwangerschaft sind sehr limitiert, und die Verabreichung dieser Substanzen in der Schwangerschaft und/oder Stillzeit ist daher zur Zeit nicht empfohlen [112] (zum Teil sehr lange Wirkdauer beachten! ).…”

Understanding the new FDA pregnancy and lactation labeling rules

“…Most of the currently available reproductive safety information on biologic drugs is derived from spontaneous reports or underpowered cohort studies, which contain inconsistent information that requires scrutiny when assessing outcomes (Calligaro et al, 2015). Postmarketing surveillance efforts have not been a priority for manufacturers in most cases, but the PLLR now requires pregnancy registries to become a routine part of postmarketing surveillance.…”