In pregnancy, which class of biologic DMARDs is considered to have no increased risk and is preferred?

• A. Rituximab
• B. IL-6 inhibitors
• C. TNF inhibitors
• D. CTLA-4 inhibitors

Answer: (C)

During pregnancy, the goal is to control the maternal disease while minimizing fetal exposure to medication. The class with the most favorable safety data for use in pregnancy is the TNF inhibitors. A large body of experience shows no clear increase in birth defects or adverse obstetric outcomes with these drugs, so they are generally preferred when biologic therapy is needed to control disease.

Within this class, there is a useful nuance: most TNF inhibitors cross the placenta to some degree, but the overall safety data still support their use. An exception is certolizumab pegol, which lacks an Fc region and has minimal placental transfer, making it particularly appealing in later pregnancy.

Other biologic classes—rituximab, IL-6 inhibitors, and CTLA-4 inhibitors—have more limited safety data in pregnancy, and concerns about fetal immunology and neonatal outcomes lead to them being avoided or used with extreme caution.