Intrauterine Exposure to Biologics in Inflammatory Autoimmune Diseases: A Systematic Review

Abstract

Background Inflammatory autoimmune diseases are chronic diseases that often affect women of childbearing age. Therefore, detailed knowledge of the safety profile of medications used for management of inflammatory autoimmune diseases during pregnancy is important. However, in many cases the potential harmful effects of medications (especially biologics) during pregnancy (and lactation) on mother and child have not been fully identified. Objective Our aim was to update the data on the occurrence of miscarriages and (major) congenital malformations when using biologics during pregnancy based on newly published articles. Additionally, we selected several different secondary outcomes that may be of interest for clinicians, especially information on adverse events in the use of a specific biologic during pregnancy. Material and Methods A search was conducted from 1 January 2015 until 4 July 2019 in Embase.com, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar with specific search terms for each database. Selection of publications was based on title/abstract and followed by full text (double blinded, two researchers). An overview was made based on outcomes of interest. References of the included publications were reviewed to include and minimize the missing publications. Results A total of 143 publications were included. The total number of cases ranged from nine for canakinumab to 4276 for infliximab. The rates of miscarriages and major congenital malformations did not show relevant differences from those rates in the general population. Conclusion Despite limitations to our study, no major safety issues were reported and no trend could be identified in the reported malformations.

A Systematic Review of the safety of non-TNF inhibitor biologic and targeted synthetic drugs in rheumatic disease in pregnancy

“…Overall, our findings agree with these other recent systematic reviews [129,130] and have not identified any evidence of an increased risk of APO compared to the general population, when considering either non-TNFI and tsDMARDs as a whole, by mode of inhibition or as individual drugs. The increasing body of evidence from ours and other recent systematic reviews should be viewed as useful adjuncts to existing guidelines/recommendations [6][7][8][9], particularly where either conditional or no recommendations could be made due to lack of evidence.…”

“…Tsao et al [129] conducted a meta-analysis of 24 studies comparing pregnancy outcomes in biologic and non-biologic exposed pregnancies and did not find any association between biologic exposure and congenital malformation, pre-term birth or low birth weight. Ghalandari et al [130] systematically reviewed 143 studies, primarily considered data on miscarriages and congenital malformations from biologic pregnancy exposures, and did not report any major safety issues. There are important methodological differences between these studies and our own, such that each yields distinct and useful information upon biologic use in pregnancy.…”

“…The metaanalysis of Tsao et al [129] calculated potential risks of all biologics as a whole and the majority (19 of 24) of articles analysed only considered TNFi biologic outcomes. The broader range of articles systematically reviewed by Ghalandari et al [130] described outcomes from pregnancy exposures to TNFi and non-TNFi biologics separately and also additional secondary outcomes such as vaccination response and detectable drug levels during different stages of conception and pregnancy. In contrast, we have focussed solely on pregnancy outcomes from exposures to non-TNFi biologics as well as tsDMARDs and considered paternal and breastfeeding exposures, as well as long-term outcomes in children potentially exposed in utero.…”

Aktuelles zur antirheumatischen Therapie bei Kinderwunsch, Schwangerschaft und Stillzeit

“…1 ) (ACR 2020: „conditionally recommended“) [ 4 ]. Dabei ist die Datenlage zu jedem einzelnen Biologikum limitiert oder nicht existent [ 42 , 43 ]. Jedoch leiten sich diese Empfehlungen von der Pharmakokinetik der monoklonalen Antikörper ab.…”

Use of inhibitors of tumor necrosis factor α in women with ankylosing spondylitis

“…Что касается безопасности иФНОα при гестации у женщин c иммуновоспалительными заболеваниями, то, по данным систематического обзора проспективных и ретроспективных исследований, выполненных в 2015-2019 гг. [12], на фоне терапии АДА, ЭТЦ, ЦЗП частота спонтанных абортов (0,4-17,4%), преждевременных родов (3,2-11,5%), врожденных пороков развития (1,9-6,2%) не отличались от общепопуляционной, что подтверждает полученные ранее сведения о профиле безопасности иФНО; серьезные инфекции были зафиксированы у 0-7,9% младенцев. У детей, матери которых получали ИНФ во время беременности, серьезные инфекции встречались в среднем в 18,2% случаев.…”