Upadacitinib in Pregnancy
Upadacitinib should be discontinued before conception and avoided throughout pregnancy due to evidence of animal teratogenicity and the requirement for effective contraception during treatment. 1, 2
Contraindication and Discontinuation Timing
- Women of childbearing age must use effective contraception during upadacitinib treatment and for 4 weeks after the final dose. 2
- The 2025 expert consensus on JAK inhibitors explicitly lists pregnancy and lactation as a contraindication (Level of Evidence 5, Strength of Recommendation D), with 100% agreement among experts. 1
- Pregnancy status must be verified before initiating upadacitinib treatment. 2
Evidence of Teratogenic Risk
Animal Studies
- Upadacitinib demonstrated dose-dependent teratogenicity in animal studies, including skeletal malformations in rats and cardiovascular malformations in rabbits at exposures as low as 0.6-1.6 times the human therapeutic dose. 2
- Specific malformations observed in rats included misshapen humerus, bent scapula, bent forelimbs/hindlimbs, and rib/vertebral defects at therapeutic-equivalent exposures. 2
- Rabbit studies showed embryolethality, increased post-implantation loss, and cardiovascular malformations at 5.6-15 times human exposure levels. 2
Human Pregnancy Data
- Available human data from 128 pregnancies with known outcomes show rates of adverse pregnancy outcomes comparable to the general population, with no clear pattern of teratogenicity identified to date. 3
- Among clinical trial pregnancies (n=80), outcomes included: 54% live births, 24% spontaneous abortions, 21% elective terminations, and one congenital malformation (atrial septal defect in a 35-week infant). 3
- Postmarketing data (n=48) showed: 46% live births, 38% spontaneous abortions, 15% elective terminations. 3
- A systematic review of 78 upadacitinib-exposed pregnancies reported 30 healthy babies, 15 terminations, 15 miscarriages, and 18 unknown outcomes, with no concerning pattern of malformations. 4
Clinical Considerations
Risk-Benefit Assessment
- Despite limited human data showing no definitive teratogenic pattern, the FDA classification and animal data mandate pregnancy avoidance. 2, 3
- The mean in utero exposure in clinical trials was only 5 weeks and 3 days, limiting conclusions about first-trimester exposure effects. 3
- For patients with inflammatory bowel disease or rheumatoid arthritis, increased disease activity itself is associated with adverse pregnancy outcomes including preterm delivery, low birth weight, and small for gestational age infants. 2
Pregnancy Surveillance
- If inadvertent exposure occurs during pregnancy, healthcare providers or patients should report to the pregnancy surveillance program at 1-800-633-9110. 2
Alternative Management
- Alternative treatments should be prioritized for women planning pregnancy or who are pregnant, given the animal teratogenicity data and contraindication status. 4
- The 4-week washout period after discontinuation allows for adequate drug clearance (approximately 10 half-lives) before conception attempts. 2