JAK inhibitors (Tofacitinib, Baricitinib, Upadacitinib)

• Not used in pregnancy — switch to a pregnancy-compatible DMARD before conception

Small-molecule inhibitors of Janus kinases (JAK1/2/3) → block cytokine-receptor signal transduction (JAK-STAT pathway).

• Unlike biologics (large antibodies), JAK-i are small molecules → cross placenta freely from early pregnancy
• JAK-STAT pathway is also involved in early embryonic cell adhesion/polarity — theoretical concern beyond just immune effects
• Manufacturer: stop ≥4 weeks before conception (tofacitinib, upadacitinib); avoid throughout pregnancy and breastfeeding

Non-pregnant

Agent-specific — not applicable in pregnancy

• AbsolutePregnancy — avoid, insufficient human safety data
• AbsoluteBreastfeeding — avoid

• ↑ infection risk (including herpes zoster)
• Venous thromboembolism
• Deranged lipids

• • Animal studies show teratogenicity and reduced fetal weight at supratherapeutic doses; human pregnancy data remain too limited to reassure.
• • Switch to a better-characterised alternative (e.g. TNF inhibitor, hydroxychloroquine, azathioprine) before planned conception.

• Strong CYP3A4 inhibitors/inducers

  Caution

  Significant level changes — dose adjustment needed

• 💡 If a patient conceives unexpectedly on a JAK inhibitor: stop promptly, switch to a pregnancy-compatible agent, and refer to obstetric medicine/rheumatology jointly — don't rely on reassurance from animal data alone.