From the Guidelines
After failure of both infliximab and vedolizumab in ulcerative colitis (UC), the recommended biologics to consider are ustekinumab (Stelara) or upadacitinib, with upadacitinib demonstrating superior efficacy in biologic-exposed patients, as shown in the 2024 study by 1.
Key Considerations
- Ustekinumab is typically administered as an intravenous induction dose of approximately 6 mg/kg, followed by 90 mg subcutaneous injections every 8 weeks for maintenance, as outlined in the study by 1.
- Upadacitinib is given orally at 10-30 mg twice daily for 8-16 weeks for induction, then 10 mg twice daily for maintenance, with the higher dose showing superior efficacy in biologic-exposed patients, as demonstrated in the study by 1.
- For patients with inadequate response to standard dosing, consider optimizing therapy by increasing the frequency of ustekinumab to every 4-6 weeks or maintaining the higher dose of upadacitinib.
- These medications work through different mechanisms than previous failed therapies - ustekinumab targets the p40 subunit shared by IL-12 and IL-23 cytokines, while upadacitinib is a JAK inhibitor that blocks multiple inflammatory pathways, as discussed in the study by 1.
Patient-Specific Factors
- The choice between these agents should consider patient-specific factors including:
- Preference for oral versus injectable therapy
- Comorbidities (particularly avoiding upadacitinib in patients with high thrombosis risk)
- Insurance coverage
- Regular monitoring for response is essential, with consideration of colectomy if medical therapy continues to fail despite optimization, as emphasized in the study by 1.
Evidence-Based Recommendation
The recommendation to use ustekinumab or upadacitinib after failure of infliximab and vedolizumab is based on the most recent and highest quality study available, which demonstrates the superior efficacy of upadacitinib in biologic-exposed patients, as shown in the 2024 study by 1. This study highlights the importance of prior treatment exposure on subsequent therapy selection in moderate-to-severe UC, and provides evidence for the use of upadacitinib as a preferred option in this population.
From the FDA Drug Label
Ustekinumab was evaluated in two randomized, double-blind, placebo-controlled clinical studies [UC-1 and UC-2 (NCT02407236)] in adult patients with moderately to severely active ulcerative colitis who had an inadequate response to or failed to tolerate a biologic (i.e., TNF blocker and/or vedolizumab), corticosteroids, and/or 6-MP or AZA therapy. A total of 51% had failed at least one biologic and 17% had failed both a TNF blocker and an integrin receptor blocker.
Recommended biologics for ulcerative colitis (UC) patients after failure of infliximab and vedolizumab:
- Ustekinumab: is a recommended biologic for UC patients who have failed infliximab and/or vedolizumab, as well as corticosteroids, and/or immunomodulators 2.
From the Research
Biologics for Ulcerative Colitis (UC) Patients After Failure of Infliximab and Vedolizumab
- Ustekinumab is a recommended biologic for the treatment of moderate-to-severe ulcerative colitis (UC) and can be considered as a therapeutic option following the failure of other biologics, including anti-tumor necrosis factor-α antagonists and anti-α4ß7 integrin antagonists 3.
- The efficacy of ustekinumab in inducing and maintaining remission in patients with moderate-to-severe UC has been demonstrated in clinical trials 4.
- A real-world comparison of the effectiveness of ustekinumab and vedolizumab in patients with UC exposed to at least one anti-TNF agent found that ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC 5.
- Other biologics approved for the treatment of UC include infliximab, adalimumab, golimumab, and vedolizumab, and the choice of biologic therapy may depend on patient-specific and disease-specific characteristics as well as biomarkers 6.
Considerations for Biologic Therapy in UC
- Therapeutic drug monitoring of biologics, especially anti-TNF alpha agents, may improve the long-term efficacy of these agents 6.
- The positioning of ustekinumab in the therapeutic strategy for UC remains unclear, and further studies are required to understand the efficacy and safety of ustekinumab in patients with UC, particularly in special situations 3.
- Primary failure to at least one biologic/small molecule was significantly associated with a decreased rate of steroid-free clinical remission among patients treated with ustekinumab 5.