What are the recommendations for using tofacitinib (Janus kinase inhibitor) in females attempting conception?

Tofacitinib Use in Females Attempting Conception

Tofacitinib should be discontinued before attempting conception due to insufficient human safety data and concerning animal studies showing teratogenic effects. 1, 2

Evidence and Recommendations

Current Guideline Position

• The American College of Rheumatology (ACR) has not established formal recommendations regarding tofacitinib use during conception attempts due to lack of sufficient safety data 3, 1
• The FDA label indicates significant concerns based on animal studies showing teratogenicity in rabbits at exposure levels 13 times the recommended dose 2
• As a small molecule, tofacitinib is likely to cross the placental barrier throughout pregnancy 3, 4

Animal Studies and Teratogenic Risk

• In rabbit embryofetal developmental studies, tofacitinib was teratogenic at exposure levels approximately 13 times the recommended dose 2
• Teratogenic effects included:
  • Thoracogastroschisis
  • Omphalocele
  • Membranous ventricular septal defects
  • Cranial/skeletal malformations (microstomia, microphthalmia)
  • Mid-line and tail defects 2

Pre-Conception Planning

• Women should discontinue tofacitinib before attempting conception 1
• Transition to pregnancy-compatible alternatives before conception 1
• Achieve disease control with pregnancy-compatible medications before attempting conception 1

Pregnancy-Compatible Alternatives

Strongly Recommended Alternatives (ACR)

• Hydroxychloroquine
• Sulfasalazine
• Azathioprine
• Colchicine
• Certolizumab 1

Conditionally Recommended Alternatives (ACR)

• Cyclosporine
• Tacrolimus
• TNF inhibitors (infliximab, etanercept, adalimumab, golimumab) 1

Management of Inadvertent Exposure

If inadvertent exposure to tofacitinib occurs during early pregnancy:

• Discontinue tofacitinib immediately
• Pursue counseling regarding potential risks
• Consider switching to pregnancy-compatible alternatives 1

Limited Human Data

• Limited case reports from tofacitinib clinical trials across various indications (RA, psoriasis, UC) show pregnancy outcomes similar to the general population 5, 6
• However, these data are insufficient to establish safety, as:
  • Sample sizes are small
  • Most exposures were brief and limited to early pregnancy
  • Long-term follow-up of exposed infants is lacking 4, 7

Important Considerations

• Female fertility may be affected by tofacitinib based on animal studies 2, 7
• The FDA label states: "Based on findings in rats, treatment with tofacitinib may result in reduced fertility in females of reproductive potential" 2
• Balance between disease control and medication risks must be considered, as active inflammatory disease itself can negatively impact pregnancy outcomes 1, 7

Paternal Exposure

• Limited data suggests paternal exposure to tofacitinib may be less concerning
• 44 reported cases showed outcomes similar to the general population 1, 6
• Additional research is needed to fully understand implications of paternal exposure