Skyrizi (Risankizumab) for Crohn's Disease
Risankizumab (Skyrizi) is FDA-approved for the treatment of moderately to severely active Crohn's disease in adults and is recommended as an effective IL-23 inhibitor option for patients who have had inadequate response to conventional therapy and/or anti-TNF therapy. 1
Mechanism of Action and Indication
- Risankizumab is an interleukin-23 antagonist that selectively targets the p19 subunit of IL-23, making it highly specific compared to other biologics that target both IL-12 and IL-23 2
- FDA-approved specifically for moderately to severely active Crohn's disease in adults, providing a targeted therapeutic option for this inflammatory bowel disease 1
Dosing Regimen
- Induction phase: 600 mg administered by intravenous infusion over at least one hour at Weeks 0,4, and 8 1
- Maintenance phase: 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every 8 weeks thereafter 1
- The FDA recommends using the lowest effective dosage needed to maintain therapeutic response 1
Efficacy in Crohn's Disease
In the phase 3 ADVANCE and MOTIVATE induction trials, risankizumab demonstrated significantly higher rates of:
In the FORTIFY maintenance trial:
- Patients receiving risankizumab 360 mg achieved 52% clinical remission vs 40% with placebo withdrawal 4
- Endoscopic response was maintained in 47% of patients on risankizumab 360 mg vs 22% on placebo 4
- A dose-response relationship was observed, with the 360 mg dose showing numerically better outcomes than the 180 mg dose for most endpoints 4
Positioning in Treatment Algorithm
Risankizumab should be considered for patients with moderate-to-severe Crohn's disease who have had inadequate response to:
The British Society of Gastroenterology (2025) supports the use of risankizumab for Crohn's disease, noting moderate certainty for a moderate benefit for induction of remission 5
Steroid-Sparing Effects
- Risankizumab demonstrates significant steroid-sparing effects:
- At week 52,50% of patients on risankizumab 360 mg were able to discontinue corticosteroids 7
- Corticosteroid-free clinical remission was achieved in approximately 50% of patients on risankizumab maintenance therapy 7
- Corticosteroid-free endoscopic response was achieved in 44.7% of patients on risankizumab 360 mg vs 20.7% on placebo 7
Safety Considerations
Prior to initiating treatment:
Common adverse events include:
Overall safety profile is favorable with no new safety signals noted in clinical trials 8, 3, 4
Monitoring Recommendations
- Monitor liver enzymes and bilirubin levels at baseline and during induction (up to at least 12 weeks of treatment) 1
- Assess clinical response between 8-12 weeks of therapy 9
- Consider endoscopic evaluation to assess mucosal healing as this correlates with better long-term outcomes 2
Comparison to Other Biologics
- Unlike TNF inhibitors, risankizumab has a low rate of immunogenicity (antibody formation under 5%) 2
- The European Crohn's and Colitis Organisation (ECCO) recommends TNF inhibitors (infliximab, adalimumab, certolizumab pegol) as first-line biologics for moderate-to-severe Crohn's disease 5
- Ustekinumab is also strongly recommended for induction and maintenance of remission in Crohn's disease with inadequate response to conventional therapy and/or anti-TNF therapy 5, 2
- The choice between risankizumab and other biologics should be based on prior treatment history, with risankizumab being particularly valuable for patients who have failed TNF inhibitors 5, 2
Practical Considerations
- When switching from IV induction to subcutaneous maintenance, ensure proper training for self-administration 1
- For patients with severe disease, consider the higher maintenance dose (360 mg) as it shows numerically better outcomes for most endpoints 4
- Risankizumab can be used as monotherapy or in combination with conventional immunomodulators 1