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World J Rheumatol. Jul 12, 2015; 5(2): 82-89
Published online Jul 12, 2015. doi: 10.5499/wjr.v5.i2.82
Safety of biologic therapies during pregnancy in women with rheumatic disease
Natalia Mena-Vazquez, Sara Manrique-Arija, Antonio Fernandez-Nebro
Natalia Mena-Vazquez, Sara Manrique-Arija, Antonio Fernandez-Nebro, Department of Rheumatology, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, 29009 Málaga, Spain
Author contributions: All the authors contributed to this paper.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Antonio Fernandez-Nebro, PhD, Department of Rheumatology, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Plaza del Hospital Civil s/nPabellón 7 – 2ª planta, 29009 Málaga, Spain. afernandezn@uma.es
Telephone: +34-951-290360 Fax: +34-951-290360
Received: August 2, 2014
Peer-review started: August 3, 2014
First decision: August 28, 2014
Revised: March 8, 2015
Accepted: April 1, 2015
Article in press: April 7, 2015
Published online: July 12, 2015
Abstract

Inflammatory rheumatic diseases frequently affect women of childbearing age. Biologic therapy during pregnancy is an important topic that is yet unresolved. The majority of documented experiences are in case series, case reports, or registries. Tumor necrosis factor (TNF) inhibitors are now better known. Some evidence suggests that it is possible that differences between drugs regarding safety are associated with the structure and capacity to cross the placenta, but we are not aware of any study that supports unequivocally this statement. Most of the monoclonal antibodies are actively transferred to fetal circulation using the neonatal Fc receptor. Although this transfer does not appear to be associated with the risk of miscarriage, stillbirth, or congenital abnormality, the rate of premature births and lower birth weight may be increased. During fetal development, the neonatal period, and childhood, the immune system is constantly maturing. The ability to produce cytokines in response to infectious stimulus remains low for years, but is similar to that of an adult around the age of 3 years owing to the adaptive nature of the newborn’s immune system as a result of exposure to microbes. Therefore, exposure to TNF inhibitors may have serious consequences on the newborn, such as severe infections or allergic reactions. Regarding the former, an anecdotal case report described a fatal case of disseminated bacillus Calmette-Guérin (BCG) infection in an infant born to a mother taking infliximab for Crohn’s disease. Although the baby was born and progressed well initially, he died at 4.5 mo after he was vaccinated with BCG. Fortunately, serious infections do not appear to be frequent in newborns exposed to in utero biologic therapy. However, very limited short-term experiences are available regarding complications in an exposed fetus, and no data are available about long-term implications on the child’s developing immune system. Therefore, we must be aware of potential complications in later years. Although the clinical data to date are promising, no firm conclusions can be drawn about the safety of biologic drugs during pregnancy, and, without further evidence, guidelines that suggest these drugs should be avoided at the time of conception cannot yet be changed.

Keywords: Pregnancy, Biologic therapy, Monoclonal antibodies, Rheumatic diseases, Safety

Core tip: Biologic therapy during pregnancy is an important topic that remains unresolved. Most of the monoclonal antibodies are actively transferred to fetal circulation using the neonatal Fc receptor. Some evidence suggests that differences may exist between drugs relating to safety associated with structure and the capacity to cross the placenta, but we are not aware of any study that supports this statement. Although the clinical data to date are promising, no firm conclusions can be drawn about the safety of biologic drugs during pregnancy, and, without further evidence, guidelines that suggest these drugs should be avoided at the time of conception cannot yet be changed.