What are the next steps for a patient with Crohn's disease and stricture who has failed treatment with Rinvoq (upadacitinib), considering IL-23 inhibition?

From the Guidelines

For Crohn's disease with strictures that has failed Rinvoq (upadacitinib) therapy, ustekinumab (Stelara) is a recommended next step, as it targets both IL-12 and IL-23 pathways and has shown efficacy in patients who have failed anti-TNF therapy 1. Ustekinumab has been studied in patients with moderate to severe Crohn's disease who have failed to achieve or maintain clinical remission with anti-TNF-based therapy, and it has been shown to induce and maintain clinical remission 1. The dose of ustekinumab for Crohn's disease is typically 6 mg/kg IV induction, followed by 90mg subcutaneous maintenance every 8 weeks. Before starting ustekinumab therapy, surgical evaluation should be considered for symptomatic strictures, as this medication may not adequately address mechanical obstruction. Additionally, other options include vedolizumab (Entyvio), which has a gut-selective mechanism, or IL-23 inhibitors like risankizumab (Skyrizi) or guselkumab (Tremfya), although the evidence for these medications in this specific context is less clear 1. Combination therapy with an immunomodulator like azathioprine or methotrexate could also be considered. Tuberculosis screening, hepatitis B testing, and assessment for active infections should be completed before initiating any new biologic therapy 1. Regular monitoring for clinical response and potential side effects will be necessary once treatment begins. It's also important to note that endoscopic dilatation is a therapeutic option for patients with Crohn's disease and symptomatic strictures, especially if the stricture is less than 4 cm 1.

Some key points to consider when treating Crohn's disease with strictures that has failed Rinvoq therapy include:

• Ustekinumab is a recommended next step due to its efficacy in patients who have failed anti-TNF therapy
• Surgical evaluation should be considered for symptomatic strictures
• Other options include vedolizumab, IL-23 inhibitors, and combination therapy with immunomodulators
• Regular monitoring for clinical response and potential side effects is necessary
• Endoscopic dilatation is a therapeutic option for patients with symptomatic strictures.

From the FDA Drug Label

INDICATIONS AND USAGE OMVOHTM is an interleukin-23 antagonist indicated for the treatment of: moderately to severely active Crohn's disease in adults Recommended Dosage for Crohn's Disease Induction Dosage: Week 0, Week 4, and Week 8: Infuse 900 mg intravenously over at least 90 minutes. Maintenance Dosage: Week 12 and every 4 weeks thereafter: Inject 300 mg subcutaneously

For a patient with Crohn's disease and stricture who failed Rinvoq, mirikizumab (OMVOH), an IL-23 antagonist, may be considered as a next step. The recommended dosage for Crohn's disease is an induction dose of 900 mg intravenously at weeks 0,4, and 8, followed by a maintenance dose of 300 mg subcutaneously every 4 weeks starting at week 12 2.

From the Research

Next Steps for Crohn's Disease with Stricture After Failed Rinvoq Treatment

• Consideration of IL-23 inhibitors as a potential next step, given their efficacy in inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe Crohn's disease 3
• Evaluation of endoscopic balloon dilation as a treatment option for strictures, which has been shown to be effective in avoiding surgery in patients with stricturing Crohn's disease 4, 5
• Assessment of the patient's overall condition and medical history to determine the best course of treatment, as intestinal strictures in Crohn's disease can be complex and require a comprehensive approach 6

IL-23 Inhibitors for Crohn's Disease

• IL-23 inhibitors have been shown to be effective in inducing clinical remission in biologic-naïve and biologic-experienced patients with Crohn's disease 3
• Targeting IL-23 has been associated with a decreased risk of serious adverse events in induction and maintenance trials compared to placebo 3
• IL-23 inhibitors may be a viable option for patients who have failed other treatments, including Rinvoq

Endoscopic Balloon Dilation for Strictures

• Endoscopic balloon dilation is a commonly used treatment for strictures in Crohn's disease, with a high success rate in avoiding surgery 4, 5
• The procedure is generally safe, with rare serious complications, and can be repeated as needed 5
• Endoscopic balloon dilation may be used in combination with other treatments, such as anti-TNF therapy, to achieve better outcomes 4