When should Skyrizi (risankizumab) be discontinued during pregnancy and why?

Skyrizi (Risankizumab) Discontinuation in Pregnancy

Skyrizi should be discontinued when pregnancy is confirmed or when planning pregnancy, as there is insufficient safety data in pregnant women and the drug is an IL-23 inhibitor that lacks established pregnancy compatibility evidence.

Timing of Discontinuation

• Discontinue Skyrizi when planning pregnancy or immediately upon pregnancy diagnosis 1
• Unlike TNF inhibitors which have robust pregnancy safety data, IL-23 inhibitors including risankizumab lack sufficient evidence to support continuation during pregnancy 2, 1

Rationale for Discontinuation

Lack of Pregnancy Safety Data

• Risankizumab (Skyrizi) is an IL-23 inhibitor with limited human pregnancy exposure data, unlike TNF inhibitors which have extensive safety profiles demonstrating no increased risk of congenital malformations or adverse pregnancy outcomes 2, 1
• Current clinical guidelines do not include IL-23 inhibitors among pregnancy-compatible biologics for inflammatory conditions 2

Placental Transfer Concerns

• Unlike certolizumab pegol (a TNF inhibitor lacking an Fc region with minimal placental transfer), risankizumab is an IgG1 monoclonal antibody that likely crosses the placenta, potentially exposing the fetus to immunosuppression 2
• IgG1-based biologics demonstrate significant placental transfer, particularly after gestational week 20, which can affect neonatal immune function and vaccination schedules 2

Alternative Pregnancy-Compatible Options

First-Line Alternatives

• TNF inhibitors are strongly recommended as pregnancy-compatible biologics that can be continued throughout pregnancy without increasing adverse outcomes 2
• Certolizumab pegol is the preferred biologic due to minimal placental transfer and no need to modify infant vaccination schedules 2, 1
• Other TNF inhibitors (infliximab, adalimumab, golimumab, etanercept) may be continued throughout pregnancy with strong evidence supporting safety 2

Additional Compatible Options

• Secukinumab (IL-17 inhibitor) may be used when needed for maternal disease control with conditional recommendation, showing no increase in adverse pregnancy outcomes 2
• Sulfasalazine and azathioprine are strongly recommended as safe disease-modifying agents throughout pregnancy 2

Clinical Management Algorithm

Pre-Conception Planning

• Discontinue Skyrizi at least several months before attempting conception to allow transition to pregnancy-compatible alternatives and confirm their efficacy 2
• Transition to certolizumab pegol or another TNF inhibitor as first-line pregnancy-compatible biologic therapy 2, 1
• Allow adequate time to establish disease control with the new agent before conception 2

If Pregnancy Discovered While on Skyrizi

• Stop Skyrizi immediately upon pregnancy confirmation 1
• Transition to pregnancy-compatible biologic therapy (preferably certolizumab pegol) if disease control is needed 2
• Coordinate care with maternal-fetal medicine specialists 2

Common Pitfalls to Avoid

• Do not continue Skyrizi during pregnancy based on lack of known harm—absence of evidence is not evidence of safety, and pregnancy-compatible alternatives with robust safety data exist 2, 1
• Do not delay switching from Skyrizi when planning pregnancy—allow several months to establish efficacy of pregnancy-compatible alternatives before conception 2
• Do not assume all biologics have similar pregnancy safety profiles—TNF inhibitors have extensive pregnancy data while IL-23 inhibitors do not 2, 1