What is the recommended treatment for Crohn’s disease using Interleukin-23 (IL-23) inhibitors?

IL-23 Inhibitors for Crohn's Disease Treatment

Ustekinumab is strongly recommended as first-line IL-23 inhibitor therapy for moderate-to-severe Crohn's disease in patients with inadequate response to conventional therapy and/or anti-TNF therapy. 1

IL-23 Inhibitor Options for Crohn's Disease

First-Line IL-23 Inhibitor

• Ustekinumab is an IgG1 monoclonal antibody that binds to the p40 subunit shared by interleukins 12 and 23 1
• Induction should be given intravenously using a weight-based regimen of approximately 6 mg/kg 1
• Maintenance dosing is administered subcutaneously 1
• Ustekinumab demonstrated high-quality evidence for induction of clinical remission with a relative risk of 1.76 (95% CI: 1.40-2.22) versus placebo 1
• Endoscopic improvement was achieved in 47.7% of patients receiving ustekinumab compared with 29.9% of those receiving placebo 1

Newer IL-23 Inhibitors

Risankizumab

• Risankizumab is a selective IL-23 p19 inhibitor recently approved for Crohn's disease 2
• Induction dosage for Crohn's disease: 600 mg administered by intravenous infusion at weeks 0,4, and 8 2
• Maintenance dosage: 180 mg or 360 mg administered subcutaneously at week 12, and every 8 weeks thereafter 2
• In phase 3 ADVANCE and MOTIVATE trials, risankizumab demonstrated significantly higher clinical remission rates versus placebo (42-45% vs 20-25%) 3
• Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated with sustained clinical remission rates >71% 4
• The FORTIFY maintenance trial showed dose-dependent efficacy with 360 mg risankizumab achieving higher clinical remission rates than 180 mg 5

Mirikizumab

• Mirikizumab is another IL-23 p19 antagonist recently approved for Crohn's disease 6
• Induction dosage: 900 mg administered by intravenous infusion at weeks 0,4, and 8 6, 7
• Maintenance dosage: 300 mg administered subcutaneously at week 12, and every 4 weeks thereafter 6, 7
• In the VIVID-1 trial, mirikizumab demonstrated superior efficacy to placebo for both induction and maintenance therapy 7
• Endoscopic response-composite was achieved in 38.0% of mirikizumab patients versus 9.0% on placebo 7

Treatment Strategy and Positioning

• IL-23 inhibitors are recommended for patients with moderate-to-severe Crohn's disease who have had an inadequate response to conventional therapy and/or anti-TNF therapy 1
• The American Gastroenterological Association (AGA) recommends ustekinumab over no treatment for the induction and maintenance of remission in moderate-to-severe Crohn's disease (strong recommendation, moderate certainty evidence) 1
• In patients who have failed TNF-α antagonists with primary nonresponse, the AGA recommends the use of ustekinumab 1
• For patients with secondary nonresponse to infliximab, the AGA recommends ustekinumab as one of the preferred options 1

Safety Considerations

• IL-23 inhibitors have favorable safety profiles compared to some other biologics 8
• Ustekinumab has a low rate of antibody formation (under 5%) 1
• For risankizumab, obtain liver enzymes and bilirubin levels prior to initiating treatment due to potential hepatotoxicity 2
• Complete all age-appropriate vaccinations before initiating IL-23 inhibitor therapy 2, 6
• Avoid use of live vaccines during treatment with IL-23 inhibitors 9
• Monitor for infections, as IL-23 inhibitors may increase infection risk 2, 6

Practical Considerations

• IL-23 inhibitors may be particularly beneficial in patients who have failed or are intolerant to TNF-α antagonists 9
• Early introduction of biologics, including IL-23 inhibitors, may be considered in patients with aggressive disease course or "high-risk" poor prognostic factors 9
• When switching from IV to subcutaneous formulations, real-world experience suggests high acceptability and comparable effectiveness 1
• For patients with severe disease, an extended induction regimen may be necessary to improve response rates 1

Monitoring Recommendations

• Monitor liver enzymes and bilirubin levels at baseline and during treatment, particularly during induction 2, 6
• Evaluate for tuberculosis prior to initiating treatment 2, 6
• Regular assessment of clinical response and remission is recommended to guide ongoing therapy 9
• Consider endoscopic evaluation to assess mucosal healing as this correlates with better long-term outcomes 1