Is Skrizi (Risankizumab) safe to use during pregnancy?

Safety of Risankizumab (Skyrizi) During Pregnancy

Risankizumab should be used with caution during pregnancy, as there are insufficient data to establish a drug-associated risk of adverse maternal or fetal outcomes, though animal studies showed increased fetal/infant loss at high doses. 1

Evidence on Risankizumab in Pregnancy

• The FDA label for Skyrizi (risankizumab) indicates that available pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes 1
• There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while treated with Skyrizi, suggesting patients should be encouraged to enroll by calling 1-877-302-2161 or visiting http://glowpregnancyregistry.com 1
• Monoclonal antibodies can be actively transported across the placenta, and Skyrizi may cause immunosuppression in the in utero-exposed infant 1

Animal Studies

• In an enhanced pre- and post-natal developmental toxicity study, pregnant cynomolgus monkeys were administered subcutaneous doses of risankizumab 1
• Increased fetal/infant loss was noted in pregnant monkeys at the 50 mg/kg dose, which resulted in approximately 5 times the exposure in humans administered the maximum recommended induction dose and 32 times the exposure to the maximum recommended maintenance dose 1
• No risankizumab-related effects on functional or immunological development were observed in infant monkeys from birth through 6 months of age 1

Considerations for Use in Pregnancy

• The background risk of major birth defects and miscarriage for women with inflammatory bowel disease is unknown, but in the U.S. general population, the estimated background risk is 2% to 4% and 15% to 20%, respectively 1
• Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease is associated with increased disease activity, including preterm delivery, low birth weight infants, and small for gestational age at birth 1
• Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses and peaks during the third trimester 1

Recommendations for Monoclonal Antibodies in Pregnancy

• According to the ERS/TSANZ Task Force Statement, monoclonal antibodies are not likely to cross the placenta in sufficient quantities to cause fetal harm and should be continued during pregnancy if required for disease control in the mother 2
• Monoclonal antibodies cross the placenta, with transport increasing as pregnancy progresses, so any potential fetal effects are likely to be greater during the second and third trimesters 2

Vaccination Considerations for Infants

• Because risankizumab may interfere with immune response to infections, risks and benefits should be considered prior to administering live vaccines to infants exposed to Skyrizi in utero 1
• A minimum of 5 months after birth should be considered before administering live virus immunizations in infants exposed in utero, because of the half-life of the product 1

Clinical Decision Making

• When considering risankizumab use during pregnancy, clinicians should compare the benefits and risks of each medication 2
• The use of any drugs during pregnancy needs to balance the maternal risk of therapy versus no therapy and the fetal risk of uncontrolled maternal disease with the risk of therapy on the newborn 2
• For inflammatory conditions requiring biologic therapy during pregnancy, the FDA classification system categorizes many biologics as Category B (animal reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women) 2

Conclusion

When considering risankizumab use during pregnancy, healthcare providers should weigh the potential benefits of controlling maternal disease against the uncertain risks to the fetus. Given the limited human data, close monitoring and enrollment in the pregnancy registry are recommended for pregnant women who require risankizumab treatment.