Tofacitinib Should Be Avoided During Pregnancy Due to Insufficient Safety Data
Tofacitinib (Xeljanz) should be avoided during pregnancy due to insufficient human safety data and concerning animal studies showing teratogenic effects. 1, 2
Current Recommendations
The 2020 American College of Rheumatology (ACR) guidelines specifically state that no recommendations can be made for tofacitinib use during pregnancy due to lack of data 1. This stands in contrast to other medications for rheumatic diseases where clear recommendations (either for or against use) are provided.
The FDA label for tofacitinib (Xeljanz) highlights several important concerns:
- Limited human pregnancy data (only 11 exposed patients in registry)
- Animal studies showing fetocidal and teratogenic effects at doses 73 times and 6.3 times the maximum recommended human dose, respectively
- Reductions in live litter size, postnatal survival, and pup body weights in animal studies 2
Mechanism of Concern
Tofacitinib is a small molecule Janus kinase (JAK) inhibitor that, due to its small molecular size, is likely to cross the placental barrier throughout pregnancy 3. This is different from larger biologic agents like certolizumab, which have minimal placental transfer, especially in early pregnancy.
Available Evidence on Pregnancy Outcomes
The limited data available comes primarily from cases where pregnancy occurred despite contraception requirements in clinical trials:
In rheumatoid arthritis and psoriasis trials, 47 pregnancies with maternal exposure were reported with outcomes including:
- 25 healthy newborns
- 7 spontaneous abortions
- 8 medical terminations
- 1 case of congenital pulmonary valve stenosis
- 6 cases pending/lost to follow-up 4
In ulcerative colitis studies, 11 cases of maternal exposure were reported with no congenital malformations 5
While these outcomes appear similar to general population rates, the sample size is too small to draw definitive conclusions about safety.
Comparison with Other JAK Inhibitors
Similar concerns exist for other JAK inhibitors. For example, upadacitinib also showed teratogenicity in animal studies, though human pregnancy data (128 cases) showed rates of adverse outcomes comparable to the general population 6.
Alternative Treatment Options During Pregnancy
The ACR guidelines provide clear recommendations for several medications that are considered safe during pregnancy:
- Strongly recommended: Hydroxychloroquine, sulfasalazine, azathioprine, colchicine, certolizumab 1
- Conditionally recommended: Cyclosporine, tacrolimus, TNF inhibitors (infliximab, etanercept, adalimumab, golimumab) 1, 7
Management Recommendations
Pre-conception planning:
- Discontinue tofacitinib before attempting conception
- Switch to pregnancy-compatible alternatives
- Achieve disease control before conception
If inadvertent exposure occurs:
- Discontinue tofacitinib immediately
- Pursue counseling regarding potential risks
- Consider switching to pregnancy-compatible alternatives
For paternal exposure:
- Limited data suggests paternal exposure may be less concerning
- 44 cases of paternal exposure reported outcomes similar to general population 4
Conclusion
Given the lack of sufficient human safety data and concerning animal studies showing teratogenic effects, tofacitinib should be avoided during pregnancy. Patients requiring immunomodulatory therapy during pregnancy should be switched to medications with established safety profiles as recommended by the ACR guidelines.
Human Perspective: The impact of active inflammatory disease on pregnancy outcomes must be considered when making treatment decisions. However, with several well-studied alternatives available, the risk-benefit analysis currently favors avoiding tofacitinib during pregnancy until more safety data becomes available.