What are the risks and recommendations for a pregnant patient or a patient planning to become pregnant while taking Tofacitinib (Xeljanz) for an autoimmune disease?

Tofacitinib During Pregnancy

Tofacitinib should be discontinued immediately if pregnancy is confirmed or when planning pregnancy, as there is insufficient human safety data and animal studies demonstrate teratogenic and fetocidal effects at clinically relevant exposures. 1

Guideline-Based Recommendations

Pre-Conception and Pregnancy Planning

• The American College of Rheumatology explicitly states "no recommendations for tofacitinib, baricitinib, apremilast due to lack of data" when addressing maternal medication use during pregnancy planning and pregnancy 1

• Discontinue tofacitinib before attempting conception if pregnancy is planned, as the lack of human safety data precludes any recommendation for continuation 1

• If a patient becomes pregnant while on tofacitinib, discontinue immediately and pursue counseling regarding potential fetal risks 1

FDA Drug Label Warnings

The FDA label for tofacitinib provides critical safety information:

• Animal studies demonstrate clear teratogenicity and fetotoxicity: In rats, tofacitinib caused external malformations (anasarca), cardiac defects (ventricular septal defects), and skeletal abnormalities at exposures 73-146 times the maximum human dose of 10 mg twice daily 2

• Post-implantation losses and reduced fetal viability occurred in animal studies, with increased early and late resorptions 2

• Postnatal effects in animals included reductions in live litter size, postnatal survival, and pup body weights at exposures 36-73 times human doses 2

• The FDA states: "It is not known if XELJANZ will harm an unborn baby" and notes that available human data from 11 exposed patients are "insufficient to draw conclusions about drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes" 2

Clinical Context: Disease Activity vs. Medication Risk

• Active autoimmune disease itself poses pregnancy risks: Published data indicate that increased disease activity in rheumatoid arthritis and ulcerative colitis is associated with preterm delivery (before 37 weeks), low birth weight (<2500 g), and small for gestational age infants 2

• Switch to pregnancy-compatible alternatives before conception: Options include hydroxychloroquine, sulfasalazine, azathioprine, certolizumab, or low-dose prednisone, all of which have strong or conditional recommendations for continuation during pregnancy 1

Available Human Data (Limited)

Clinical Trial and Postmarketing Data

The limited human experience includes:

• Rheumatoid arthritis/psoriasis trials: 47 maternal exposures reported 25 healthy newborns, 7 spontaneous abortions, 8 medical terminations, 1 congenital pulmonary valve stenosis, and 6 pending/lost to follow-up 3

• Ulcerative colitis trials: 11 maternal exposures resulted in healthy newborns as the most common outcome, with 2 spontaneous abortions, 2 medical terminations, and no congenital malformations or fetal deaths 4

• These small case series cannot establish safety: The numbers are far too limited to draw definitive conclusions, and the FDA explicitly states data are insufficient 2

Comparison to Other JAK Inhibitors

• A 2024 analysis of upadacitinib (another JAK inhibitor) with 128 pregnancies showed rates of adverse outcomes comparable to the general population, but this does not establish safety for tofacitinib as each drug must be evaluated independently 5

Paternal Exposure

• Paternal exposure to tofacitinib appears safer: 44 cases of paternal exposure in RA/psoriasis trials showed 23 healthy newborns, 5 spontaneous abortions, and 16 pending/lost to follow-up 3

• No specific recommendations exist from the American College of Rheumatology regarding paternal tofacitinib use, unlike the strong recommendations to discontinue cyclophosphamide and thalidomide 1

• Given the lack of data and the general safety pattern of paternal medication exposure, continuation during partner's pregnancy may be reasonable, but this should be discussed with the patient 1

Breastfeeding Considerations

• The American College of Rheumatology provides no recommendation for tofacitinib during breastfeeding due to lack of data 1

• Tofacitinib is a small molecule (molecular weight ~312 Da) that likely transfers into breast milk, as demonstrated in lactating rats 6

• The FDA recommends deciding between breastfeeding or taking tofacitinib, stating "you should not do both," and advises waiting 18 hours after the last dose before resuming breastfeeding 2

• Avoid breastfeeding while on tofacitinib given the lack of human safety data and potential for infant exposure 6

Clinical Algorithm for Management

If Patient is Planning Pregnancy:

1. Assess disease activity and severity 2
2. Transition to pregnancy-compatible medication (hydroxychloroquine, sulfasalazine, azathioprine, certolizumab, or prednisone) at least 1-3 months before attempting conception 1
3. Discontinue tofacitinib once disease is controlled on alternative therapy 1
4. Ensure effective contraception until medication transition is complete 2

If Patient Becomes Pregnant While on Tofacitinib:

1. Discontinue tofacitinib immediately 1
2. Provide counseling regarding animal teratogenicity data and limited human safety information 2
3. Transition to pregnancy-compatible immunosuppression if needed for disease control 1
4. Arrange high-risk obstetric follow-up for monitoring 2
5. Document exposure timing and duration for pregnancy registry reporting 3, 4

If Patient Wishes to Breastfeed:

1. Do not breastfeed while taking tofacitinib 2, 6
2. Wait 18 hours after last dose before initiating breastfeeding if tofacitinib has been discontinued 2
3. Consider pregnancy-compatible alternatives that are safe during lactation (hydroxychloroquine, certolizumab, TNF inhibitors) 1

Critical Pitfalls to Avoid

• Do not assume tofacitinib is safe based on limited case reports: The small numbers cannot establish safety, and animal data show clear teratogenic potential 2, 3, 4

• Do not continue tofacitinib during pregnancy "to control disease activity": Pregnancy-compatible alternatives exist and should be used instead 1

• Do not confuse the safety profile of biologics with small molecules: Unlike large monoclonal antibodies that have limited first-trimester placental transfer, tofacitinib as a small molecule likely crosses the placenta throughout pregnancy 6

• Do not rely on the "similar to general population" outcomes in small case series: These are underpowered to detect teratogenic signals, and the FDA explicitly states data are insufficient 2