IL-23 Inhibitors for Crohn's Disease Treatment

IL-23 Inhibitor Options for Crohn's Disease

• 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, with a relative risk of 1.76 (95% CI: 1.40-2.22) versus placebo 1, 2
• Ustekinumab is an IgG1 monoclonal antibody that binds to the p40 subunit shared by interleukins 12 and 23, and induction should be given intravenously using a weight-based regimen of approximately 6 mg/kg 1
• Maintenance dosing of Ustekinumab is administered subcutaneously, with endoscopic improvement achieved in 47.7% of patients receiving ustekinumab compared with 29.9% of those receiving placebo 2, 1

Treatment Strategy and Positioning

• 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) 3
• 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, with the AGA recommending ustekinumab for patients who have failed TNF-α antagonists with primary nonresponse 1, 4

Safety Considerations

• Ustekinumab has a low rate of antibody formation (under 5%) 2
• Avoid use of live vaccines during treatment with IL-23 inhibitors 5

Practical Considerations

• When switching from IV to subcutaneous formulations, real-world experience suggests high acceptability and comparable effectiveness 6
• For patients with severe disease, an extended induction regimen may be necessary to improve response rates 6

Monitoring Recommendations

• Regular assessment of clinical response and remission is recommended to guide ongoing therapy 5
• Consider endoscopic evaluation to assess mucosal healing as this correlates with better long-term outcomes 1

Treatment of Moderately to Severely Active Crohn's Disease

Positioning in Treatment Algorithm

• The British Society of Gastroenterology recommends risankizumab for Crohn's disease, noting moderate certainty for a moderate benefit for induction of remission in patients with moderate-to-severe Crohn's disease who have had inadequate response to conventional therapies or previous biologic therapies, particularly TNF inhibitors 7
• Risankizumab should be considered for patients with moderate-to-severe Crohn's disease who have had inadequate response to conventional therapies or previous biologic therapies, particularly TNF inhibitors, as supported by the British Society of Gastroenterology 7

Comparison to Other Biologics

• The European Crohn's and Colitis Organisation recommends TNF inhibitors as first-line biologics for moderate-to-severe Crohn's disease, and 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 8, 9, 10

Treatment of Crohn's Disease with IL-23 Inhibitors

Introduction to IL-23 Inhibitors

• The American Gastroenterological Association recommends IL-23 inhibitors, including risankizumab, for patients with moderate-to-severe Crohn's disease who have failed anti-TNF therapy, with strong recommendation and moderate-quality evidence 11, 12
• Patients with documented failure of two different biologic classes, such as anti-TNF and anti-integrin, may benefit from switching to an IL-23 inhibitor as the next therapeutic option, as recommended by the Clinical Gastroenterology and Hepatology society 11, 12

Treatment Sequencing and Efficacy

• The Clinical Gastroenterology and Hepatology society recommends switching to an IL-23 inhibitor after failure of anti-TNF therapy, with strong recommendation and moderate-quality evidence 11, 12
• Vedolizumab failure in patients who have not responded well after switching from anti-TNF therapy represents an appropriate indication to switch out of class to an IL-23 inhibitor, as recommended by the Gut society 11, 13

Safety Considerations

• The FDA requires liver enzymes and bilirubin levels to be obtained prior to initiating Skyrizi for Crohn's disease, and recommends against using corticosteroids for maintenance of remission, with strong recommendation 14
• The Clinical Gastroenterology and Hepatology society recommends evaluating vedolizumab response between 10-14 weeks, and switching to an IL-23 inhibitor if there is inadequate response, with strong recommendation and moderate-quality evidence 11, 12

Alternative Therapies

• Ustekinumab is another reasonable IL-23 pathway inhibitor option for patients who fail anti-TNF therapy, with strong recommendation from the Clinical Gastroenterology and Hepatology society 11, 12, 13
• Switching to a different anti-TNF after adalimumab failure is generally less effective than switching to a different mechanism of action, as recommended by the Gut society 11, 15

Medical Necessity Assessment for Skyrizi (Risankizumab) in Refractory Crohn's Disease

Rationale for Medical Necessity

• The Canadian Association of Gastroenterology strongly recommends ustekinumab for patients with moderate to severe Crohn's disease who fail to achieve complete remission with anti-TNF therapy, and this principle applies to risankizumab as an IL-23 inhibitor (strong recommendation, moderate-quality evidence) 16, 17
• The patient's documented inadequate response to vedolizumab, including persistent symptoms and steroid-dependent pattern, constitutes treatment failure, according to the Canadian guidelines (strong recommendation, low-quality evidence) 16, 17
• The Canadian guidelines suggest evaluating vedolizumab response between 10-14 weeks to determine the need to modify therapy, and the patient has been on Entyvio for multiple months, providing adequate time to assess response 16, 17
• The Canadian guidelines recommend against corticosteroids for maintenance of remission (strong recommendation, low-quality evidence), making the patient's steroid-dependent pattern a clear indication for escalation to alternative biologic therapy 18

Clinical Algorithm for This Decision

• Verify adequate trial duration: Entyvio used for several months (adequate for assessment per 10-14 week guideline timeframe) 16, 17

Safety Considerations and Pre-Treatment Requirements

• Waiting for "complete failure" or hospitalization is not recommended—the steroid-dependent pattern and persistent symptoms already constitute treatment failure requiring escalation 16, 18