Moderately to Severely Active Crohn's Disease When Anti-TNF Therapy Has Not Achieved Remission
This protocol applies to patients with moderately to severely active Crohn's disease who carry features associated with a higher risk of disease progression and in whom prior anti-TNF–based therapy failed to achieve the target clinical and endoscopic outcomes.
Higher-Risk Clinical Features
Patients in this scenario present with moderate-to-severe active disease — characterised by symptoms such as fever, significant weight loss, and abdominal pain or tenderness — and one or more markers of higher progression risk:
- Young age at diagnosis
- Ileal or ileocolonic disease location
- Extensive disease
- Large or deep ulcers on endoscopy
Why This Protocol Is Needed — Prior Therapy Did Not Meet Goals
The previous treatment line used advanced therapy, with the preferred approach being combination infliximab and an immunomodulator; alternatives included other anti-TNF agents (adalimumab, certolizumab pegol) or other advanced biologics. The goal was durable, steroid-free clinical and endoscopic remission — CDAI below 150 with no mucosal ulceration — achieved within 12 weeks and sustained. When those thresholds are not met, escalation to this protocol is indicated.
Next-Line Approach (Partial Overview)
For patients with prior anti-TNF exposure, evidence-based options for both induction and maintenance of remission are available, including a targeted oral agent and a biologic class that is preferred over earlier biologic agents in this setting — with agent selection guided by the specific clinical profile. The full regimen, sequencing, and decision criteria are in the complete protocol.
Treatment Goals
The primary targets are clinical remission (CDAI score below 150) and endoscopic response, assessed at week 12 (end of induction) and week 52 (maintenance).
References
DOI: 10.14309/ajg.0000000000003465;
- Individuals are considered to have moderate–severe disease if they have not responded to treatment for mild–moderate disease or if they present with more prominent symptoms such as fever, significant weight loss, abdominal pain or tenderness, intermittent nausea or vomiting.
- We recommend upadacitinib use for induction and maintenance of remission for patients with moderate-to-severe CD who have previously been exposed to anti-TNF agents (strong recommendation, moderate level of evidence).
- We recommend the use of risankizumab as compared with ustekinumab in patients with moderate to severe CD and prior exposure to anti-TNF therapy (conditional recommendation, low level of evidence).
- The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a CDAI score of <150) and endoscopic response.
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