Can I Use JAK Inhibitors During Pregnancy? Save

In 2020, the ACR Recommendations on Reproductive Health notably avoided firm guidance on the use of JAK inhibitors (JAKi) during pregnancy stating, "There is no available evidence regarding use or safety of the new small- molecule agents, tofacitinib, baricitinib, and apremilast, during pregnancy."

Small molecule therapies will cross the placenta and will be in breast milk.  

Even though these agents have been commercially available for 6-12 years, their use in pregnancy has not been systematically studied. The current package inserts for commercially available JAK inhibitors advise against use during pregnancy or lactation, noting there is insufficient data (from clinical trials, registries or literature) to draw conclusions about a drug‑associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Upadacitinib PI suggests that pregnancy testing be considered prior to use of upadacitinib. Concern also comes from embryonic animal studies showing that higher doses may be feticidal and teratogenic.

A 2025 scoping review of guidelines on Disease‐Modifying Antirheumatic Drugs (DMARD) in pregnancy noted there were 6 guidelines with recommendations for tsDMARD use in pregnancy; finding low‐level to no evidence to support use and all guidelines recommending "avoiding tsDMARDs due to insufficient data on use in pregnancy." 

A recent VigiBase, World Health Organization global pharmacovigilance database, report on JAKi and pregnancy found 213 pregnancy-related ADRs - spontaneous abortion was the most frequently reported event (48%). Congenital anomalies were reported in 16% (43 events), but no specific organ-related pattern identified. Prematurity was seen in 9.2% of reports. No disproportionate increase in reports of spontaneous abortion or prematurity following JAKI exposure were seen. 

In the American Journal of Gastroenterology, Mahadevan et al reported a small cohort experience with tofacitinib during pregnancy (Maternal or Paternal Exposure). They concluded that "tofacitinib should not be used during pregnancy unless clearly necessary."  They reported on 184 pregnancies:

• 85 maternal exposure events: 46 healthy newborns, 12 medical terminations, 1 fetal death, 1 congenital malformation, 14 spontaneous abortions, and 11 pending/lost to follow-up.
• 99 paternal exposure events: 67 healthy newborns, 1 fetal death, 9 spontaneous abortions, and 22 pending/lost to follow-up
• These results were similar to that expected in the general population.

Similarly, a gastroenterology Global Consensus Consortium (39 IBD and content experts) concluded that JAK inhibitors should be avoided during pregnancy, owing to a lack of good data. Moreover, they suggest that women who wish to conceive should be off of these agents for at least 4 weeks prior ot conception, unless there is no effective alternative therapy to maintain maternal health.  SImilarly, JAK inhibitors should be avoided during breastfeeding. 

There are registries collecting data on pregnancies outcomes with JAK inhibitor exposure; these include:

• MotherToBaby Pregnancy Studies
• WHO global pharmacovigilance database (VigiBase)
• Rinvoq Pregnancy Surveillance Program: contact the manufacturer or call 1-800-633-9110.