Safety of Immunomodulators and Anti-TNF Therapy in Pregnancy

Abstract

Biologics have proved to be extremely effective therapies for active, difficult to treat ulcerative colitis and Crohn's disease. Given that active disease appears to be what drives worse outcomes in conception and pregnancy, understanding of the potential risks of continued biologic therapy during pregnancy is important. Knowledge of the mechanisms of placental transfer helps clinicians explain to patients the timing of potential cessation of therapy, and the ongoing data collection from the efforts of the Crohn's and Colitis Pregnancy Registry have helped immensely to move this field forward. The body of evidence for use of thiopurines as well has supported their continued use during pregnancy in patients, despite their category D rating. Family planning and counseling have come a long way with our efforts in understanding that the real enemy is active inflammation, not the therapies we use to treat it.

Challenges in the treatment of Rheumatoid Arthritis

“…Methotrexate (MTX) is known to be teratogenic and to induce miscarriages; it should be stopped 3 months before a planned pregnancy [64,69] and should be avoided in lactating women as small amount in breast milk has been detected. TNF inhibitors may be continued at least in the first half of pregnancy as their use has not been associated with congenital abnormalities or adverse pregnancy outcome [70,71]. Infliximab, Adalimumab and Etanercept demonstrated binding to the fetal Fc receptor (FcRn) and were actively transported across the placenta, while Certolizumab Pegol showed no measurable transfer from the maternal to the fetal circulation because of its different molecular structure that does not contain any Fc region [71].…”

“…TNF inhibitors may be continued at least in the first half of pregnancy as their use has not been associated with congenital abnormalities or adverse pregnancy outcome [70,71]. Infliximab, Adalimumab and Etanercept demonstrated binding to the fetal Fc receptor (FcRn) and were actively transported across the placenta, while Certolizumab Pegol showed no measurable transfer from the maternal to the fetal circulation because of its different molecular structure that does not contain any Fc region [71]. Evidence for fetal/ child safety is still lacking for golimumab, abatacept and rituximab, but registry data do not suggest any evidence of harm when used before conception or in the first trimester [70].…”

Pregnancy and rheumatoid arthritis

“…The use of TNF inhibitors has not been associated with congenital abnormalities or adverse pregnancy outcome [94,95]. However, very recently a prospective study from the European Network of Teratology Information Services on 495 pregnancies that were exposed to TNF-inhibitors during first trimester and 1532 pregnancies from healthy pregnant women revealed a small increase in major birth defects (5% vs1,5%; OR 2.2 95% CI 1.0-4.8).…”

Use of TNF-inhibitors and ustekinumab for psoriasis during pregnancy: A patient series

“…IgG is the only antibody to be transported from mother to fetus through the placenta. Maternal IgG antibodies are actively transported via Fc receptors on the syncytiotrophoblast and cannot cross the placenta by simple diffusion being large (>100 kDa) hydrophilic proteins (Chaudrey & Kane, ; de Lima, Zelinkova, van der Ent, Steegers, & van der Woude, ; Ruiz, Manubens, & Puig, ). Fc‐receptors have been found to appear after Week 14 of gestation and the active transportation of IgG antibodies starts in the second trimester, increasing throughout the third trimester.…”