Is infliximab (Remicade) more effective than Rinvoq (upadacitinib) at achieving mucosal healing in patients with inflammatory bowel disease (IBD), such as Crohn's disease or ulcerative colitis?

Direct Comparison: Infliximab vs Upadacitinib for Mucosal Healing

No head-to-head trials directly compare infliximab to upadacitinib (Rinvoq) for mucosal healing in IBD, but based on available evidence, infliximab demonstrates robust, well-established efficacy for achieving mucosal healing with decades of validation, while upadacitinib represents a newer agent with emerging but less extensive mucosal healing data.

Evidence for Infliximab's Mucosal Healing Efficacy

Ulcerative Colitis

• In the ACT-1 and ACT-2 trials, patients achieving mucosal healing (Mayo endoscopic subscore 0-1) with infliximab at week 8 had significantly lower colectomy rates, with 95% remaining colectomy-free compared to 80% without mucosal healing (p=0.004) 1
• Mucosal healing with infliximab at week 8 increases the likelihood of clinical remission at 30 weeks fourfold 1
• Endoscopic mucosal healing achieved with infliximab is associated with lower risks of hospitalization, colectomy, and subsequent immunosuppressive use 1

Crohn's Disease

• Sub-studies of ACCENT-1 demonstrated that patients achieving mucosal healing (absence of mucosal ulcerations) with infliximab had longer relapse-free survival and required fewer disease-related hospitalizations and surgeries 1
• In the SONIC trial sub-study, patients achieving mucosal healing at week 26 with infliximab were more likely to maintain steroid-free clinical remission at week 50 (76% vs 58%) 1
• Complete mucosal healing with infliximab was associated with sustained clinical benefit in 64.8% vs 39.5% without healing (p=0.0004), fewer hospitalizations (42.2% vs 59.3%, p=0.0018), and reduced need for major surgery (14.1% vs 38.4%, p<0.0001) 1

Evidence for Upadacitinib (Rinvoq)

Available Data

• Upadacitinib has been approved for moderately to severely active Crohn's disease in patients with inadequate response or intolerance to TNF inhibitors 2
• The American Gastroenterological Association suggests ustekinumab or tofacitinib (not upadacitinib specifically) as first-line alternatives to infliximab for ulcerative colitis 2
• No specific mucosal healing rates for upadacitinib are provided in the available guideline evidence

Critical Clinical Decision Framework

When Infliximab is Appropriate

• First-line therapy: Infliximab remains a validated first-line option with extensive mucosal healing data spanning both UC and CD 1
• Baseline elevated CRP: Infliximab effects are significantly more pronounced in patients with elevated baseline CRP levels and baseline mucosal lesions 1
• Combination with extraintestinal manifestations: Monoclonal antibody TNF inhibitors (including infliximab) are strongly recommended for patients with both axial spondyloarthritis and IBD 2

When Upadacitinib May Be Considered

• TNF-inhibitor experienced patients: Upadacitinib is approved specifically for patients with inadequate response or intolerance to one or more TNF inhibitors in Crohn's disease 2
• Contraindication to TNF antagonists: If class-wide TNF antagonist concerns exist, switch to a different mechanism of action 2
• Paradoxical reactions to infliximab: Switching within the anti-TNF class is contraindicated; mechanism switch required 3

Important Caveats and Pitfalls

Monitoring Requirements

• Mucosal healing assessment requires endoscopy at standardized timepoints: week 8 for UC with infliximab, week 26 for CD 1
• Symptomatic improvement does not equal mucosal healing; objective endoscopic assessment is mandatory 1
• Fecal calprotectin and CRP can serve as surrogate markers but do not replace endoscopic confirmation 1

Definition Variability

• Mucosal healing definitions vary across studies: some use absence of ulcerations, others use validated scores (CDEIS <4, SES-CD <3, Mayo subscore 0-1) 1
• For UC, Mayo endoscopic subscore of 0 or UCEIS score ≤1 represents mucosal healing 1
• For CD, absence of mucosal ulcerations or SES-CD <3 defines mucosal healing 1

Long-Term Outcomes

• Achieving mucosal healing changes natural disease course by decreasing relapse rates, hospitalization, and surgery in both UC and CD 1
• Histologic healing may be the ultimate therapeutic goal in UC, though its impact on CD course remains unknown 4
• Mucosal healing is associated with lower risk of colitis-associated neoplasia in UC (odds ratio 0.38, p=0.003) 1

The evidence base for infliximab's ability to achieve mucosal healing is substantially more robust and validated across multiple large trials with long-term outcome data, while upadacitinib represents a newer alternative with less extensive mucosal healing evidence in the available literature.