Moderate-to-Severe Ulcerative Colitis When an Advanced Therapy Has Not Achieved Response
This protocol applies to adult outpatients with moderate-to-severe ulcerative colitis who have previously been exposed to one or more advanced therapies — particularly TNF antagonists — and whose current treatment course has not met the expected therapeutic targets.
Clinical Scenario
Adult outpatient with moderate-to-severe UC; prior exposure to one or more advanced therapies, particularly TNF antagonists. The patient completed a standard induction course but did not achieve the targets required to continue on the current treatment plan without adjustment.
Why This Protocol — Prior Advanced Therapy Did Not Achieve
The previous treatment — a higher-efficacy agent (tofacitinib, upadacitinib, or ustekinumab) or an intermediate-efficacy agent (filgotinib, mirikizumab, risankizumab, or guselkumab), or in selected patients infliximab or golimumab — was expected to reach:
- Symptomatic response within 3 months of initiation
- Symptomatic and biochemical (clinical) remission within 3–6 months (Mayo Clinic score <3, no individual subscore >1)
- Endoscopic improvement or remission within 6–12 months
Failure to reach these targets is the trigger for the approach described below.
Next-Step Approach (Overview)
When a standard induction course has not produced sufficient response, an extended induction or dose-escalation strategy may be considered — allowing a longer duration of treatment to achieve clinical benefit, particularly for lower-efficacy medications in patients with multiple prior biologic failures. The specific agents, durations, and decision points are detailed in the full structured protocol…
Treatment Target
Clinical response or clinical remission by the end of the extended induction period (around week 16).
References
DOI: 10.1053/j.gastro.2024.10.001
- In adult outpatients with moderate-to-severe UC who have previously been exposed to 1 or more advanced therapies, particularly TNF antagonists, the AGA suggests using a HIGHER efficacy medication (tofacitinib, upadacitinib, ustekinumab) OR an INTERMEDIATE efficacy medication (filgotinib, mirikizumab, risankizumab, guselkumab), rather than a LOWER efficacy medication (adalimumab, vedolizumab, ozanimod, etrasimod).
- Lower-efficacy medications may require longer duration of treatment for response in patients with multiple prior biologic failures.
- Thus, in patients with multiple prior biologic failures, a longer duration of treatment may be required for clinical benefit for treatments in the lower-efficacy category.
- Among patients who did not respond to the 10-mg twice daily dose of tofacitinib at week 8 in the OCTAVE trial, 52% achieved clinical response at week 16 after extended induction with 10-mg twice daily dosing for an additional 8 weeks.
- Nearly one-half (48%) of patients who failed to respond to the initial 8-week induction regimen with upadacitinib 45 mg/d responded to an additional 8 weeks of induction therapy.
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