From the Guidelines
For a patient with ulcerative colitis who has failed Stelara (ustekinumab), the most appropriate next step is to switch to a different biologic agent, with upadacitinib being a superior option due to its higher efficacy in biologic-exposed patients, as demonstrated in the 2024 American Gastroenterological Association evidence synthesis 1.
Treatment Options
The treatment options for a patient with ulcerative colitis who has failed Stelara (ustekinumab) include:
- Switching to a different biologic agent such as vedolizumab (Entyvio) or a JAK inhibitor like tofacitinib (Xeljanz) or upadacitinib
- Trying a different TNF inhibitor like adalimumab (Humira) or infliximab (Remicade), especially if the patient hasn't previously failed these medications
- Surgical intervention with colectomy for patients with severe disease not responding to medical therapy
Mechanism of Action
These alternative treatments work through different mechanisms of action, including:
- Vedolizumab, which specifically targets gut lymphocyte trafficking
- JAK inhibitors, which block multiple inflammatory pathways intracellularly
- TNF inhibitors, which target a different inflammatory cytokine than Stelara, and may provide efficacy when IL-12/23 inhibition has failed
Dosing and Administration
The dosing and administration of these alternative treatments vary:
- Vedolizumab is typically administered as an intravenous infusion of 300 mg at weeks 0,2, and 6, followed by maintenance dosing every 8 weeks
- Tofacitinib is given orally at 10 mg twice daily for induction therapy for 8-16 weeks, followed by 5 mg twice daily for maintenance
- Upadacitinib is given orally at a dose that is not specified in the provided evidence, but is likely to be similar to tofacitinib
Prior to Switching Therapies
Before switching therapies, it's essential to:
- Confirm active inflammation through endoscopy or biomarkers like fecal calprotectin
- Rule out complications like infections
- Ensure optimal dosing of the current medication According to the AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis, the use of infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab is recommended over no treatment for the induction and maintenance of remission in adult outpatients with moderate-severe ulcerative colitis 1. Additionally, the AGA suggests using infliximab or vedolizumab rather than adalimumab for induction of remission in adult outpatients with moderate-severe ulcerative colitis who are naïve to biologic agents 1. However, the most recent evidence from the 2024 American Gastroenterological Association evidence synthesis suggests that upadacitinib is a superior option for biologic-exposed patients 1.
From the FDA Drug Label
Among the ENTYVIO-treated patients who developed persistent anti-vedolizumab antibodies, 14/20 patients had serum vedolizumab trough concentrations that were markedly reduced or undetectable and 15/20 patients did not achieve clinical remission at Week 52 in UC Trials I and II and CD Trials I and III The safety and efficacy of intravenous ENTYVIO were evaluated in two randomized, double-blind, placebo-controlled trials (UC Trials I and II) in adult patients with moderately to severely active ulcerative colitis (UC) defined as Mayo score of 6 to 12 with endoscopy subscore of two or three Enrolled patients in the U.S. had over the previous five-year period an inadequate response or intolerance to immunomodulator therapy (i.e., azathioprine or 6-mercaptopurine) and/or an inadequate response, loss of response, or intolerance to a TNF blocker.
For a patient with ulcerative colitis who has failed Stelara (ustekinumab), the next steps may include:
- Considering treatment with vedolizumab (ENTYVIO), as it has been shown to be effective in patients with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to immunomodulator therapy and/or a TNF blocker.
- Evaluating the patient's Mayo score and endoscopy subscore to determine the severity of their disease and potential response to treatment.
- Monitoring for anti-vedolizumab antibodies, as patients who develop persistent antibodies may have reduced serum vedolizumab trough concentrations and may not achieve clinical remission. 2
From the Research
Treatment Options for Ulcerative Colitis After Stelara (Ustekinumab) Failure
- For patients with ulcerative colitis who have failed Stelara (ustekinumab), several treatment options are available, including infliximab, vedolizumab, and adalimumab 3.
- A systematic review and meta-analysis found that infliximab and vedolizumab may be preferred as second-line biologic therapies, while adalimumab may not be the primary choice 3.
- Another study found that ustekinumab dose intensification may be effective for patients with suboptimal clinical response to standard dosing 4.
Comparative Effectiveness of Biologic Agents
- A propensity-matched cohort study found that ustekinumab may be the preferred second-line therapy over tofacitinib and vedolizumab in patients with ulcerative colitis who were previously exposed to a TNF inhibitor 5.
- A multicenter cohort study found no difference in efficacy and safety between vedolizumab and ustekinumab in patients with ulcerative colitis after anti-TNF therapy failure 6.
- A prospective, observational study found that ustekinumab showed higher treatment persistence but no significant difference in maintenance effectiveness compared to anti-TNF or vedolizumab in ulcerative colitis 7.
Considerations for Treatment Selection
- The choice of treatment should be individualized based on patient characteristics, disease severity, and prior treatment history 3, 5.
- Further studies are needed to determine predictive factors of efficacy for biologic agents in ulcerative colitis 6, 7.
- Treatment outcomes, including clinical remission, steroid-free remission, and treatment persistence, should be closely monitored to guide treatment decisions 3, 7.