LAUSR

Background Tocilizumab is a monoclonal antibody that interrupts interleukin-6 signaling, reducing downstream effects on inflammation and the innate immune response. It was shown to reduce mortality in patients with severe or critical COVID-19. Pregnant and breastfeeding people were largely excluded from clinical trials and hence, the extent to which results can be applied to these populations is not clear. Objectives To synthesize published data on tocilizumab in pregnancy and lactation, highlight important knowledge gaps, and help inform clinical decision-making about tocilizumab’s use in these populations with COVID-19. Sources PubMed was searched for studies evaluating tocilizumab in pregnancy and lactation for COVID-19 and other indications. Literature on pharmacokinetics and reproductive/fetal safety of monoclonal antibodies in general was also sought. US FDA and EMA guidance for the industry and regulatory approval documents were reviewed. Content Published data on tocilizumab in pregnancy includes 610 cases (n=20 with COVID-19) together with 7 mother-infant breastfeeding pairs. Higher rates of spontaneous abortion and premature birth have been reported compared to the general population, but multiple confounding variables limit interpretation. There is little data on tocilizumab exposure in the second and third trimesters when transplacental transport is highest. The effects of tocilizumab on the developing immune system are unclear. Pregnant patients with COVID-19 who received tocilizumab were often critically ill and corticosteroid use was uncommon. Neonatal follow-up was limited. Tocilizumab appears to be compatible with breastfeeding. Implications Although the available data do not raise serious safety signals, they have significant limitations and are not sufficient to delineate the complete spectrum of potential adverse outcomes that may be associated with tocilizumab exposure during pregnancy and lactation. Diligent follow-up and documentation of pregnancy outcomes will be important moving forward. A more effective regulatory framework to ensure equitable inclusion of pregnant people in research is clearly needed.