Two MothertoBaby/OTIS studies investigating pregnancy out¬comes in women with chronic inflammatory diseases after exposure to anti-TNFs (etanercept and adalimumab) have so far been completed. The final publications for these studies are expected immi¬nently . An increase in major birth defects with etanercept compared with disease-matched groups was indi¬cated (2005-2012; n = 370 exposed; aOR: 2.77; 95% CI, 1.04-7.35; Chambers et al., 2015). However, a drug-related effect was not sup¬ported due to the lack of a specific pattern of defects and the minimal placental transfer of etanercept anticipated in early pregnancy (Chambers et al., 2015).
In another recent observational multi-country registry study (Sweden, Denmark, and Finland), no increased risk of birth defects, preterm birth, or infections was observed in the offspring of mothers with chronic inflammatory diseases who were treated with etanercept (n = 425 pregnancies exposed during the first trimester) compared with mothers who were treated with nonbiologic systemic treatment (n = 3508) during pregnancy. The odds ratio for major birth defects in women exposed to etanercept during the first trimes¬ter compared with nonbiologic treatment during pregnancy was 0.96 (95% CI, 0.58-1.60) when adjusted for country, maternal disease, par¬ity, maternal age, and smoking status in early pregnancy . The adalimumab MothertoBaby/OTIS study (2004-2014; n = 257 exposed; aOR for major birth defects: 0.91; 95% CI, 0.37-2.23]) also found no evidence of a specific pattern of major birth defects in the exposed cohort (Chambers et al., 2017). Furthermore, the results of this study were reassuring for every outcome examined, including spontaneous abortion and preterm delivery (Chambers et al., 2017).
A recent update article on biologic safety for patients with Psoriasis during pregnancy recommends that infants born to mothers treated with anti-TNF therapies during pregnancy should not be adminis¬tered live vaccinations (e.g., Bacillus Calmette-Guerin (BCG) or rota¬virus vaccines) for at least 6 months after birth due to an increased risk of infection (Porter et al., 2017),3 advice that is also included in the drug package inserts. The only anti-TNF label that differs with re¬spect to vaccination recommendations is that of CZP, based on data demonstrating that CZP levels are undetectable at weeks 4 and 8 after delivery in the plasma of infants exposed in utero (Mariette et al., 2018). Accordingly, the U.S. and EU CZP labels state that the theoretical risk of live or live-attenuated vaccine administration to infants exposed to CZP in utero should be weighed against the benefits of these vaccinations (European Medicines Agency, 2018; U.S. Food and Drug Administration, 2018). Inactive vaccinations can be administered per routine practice