Landmark Trial: UC-SUCCESS
The UC-SUCCESS trial is the landmark study that demonstrated combination therapy of infliximab plus azathioprine was superior to either monotherapy in ulcerative colitis, achieving 39.7% corticosteroid-free remission at week 16 compared to 22.1% with infliximab alone and 23.7% with azathioprine alone. 1
Key Trial Details
The UC-SUCCESS trial was a randomized, double-blind study in anti-TNF-naïve adults with moderate to severe ulcerative colitis that compared three arms: 1
- Infliximab monotherapy (5 mg/kg at weeks 0,2,6, and 14)
- Azathioprine monotherapy (2.5 mg/kg daily)
- Combination therapy (infliximab plus azathioprine)
The trial enrolled 239 patients and was terminated prematurely before reaching enrollment targets, which limited the ability to complete the planned maintenance phase. 2, 1
Primary Outcome Results
Corticosteroid-free remission at week 16 (the primary endpoint): 1
- Combination therapy: 39.7% (31/78 patients)
- Infliximab monotherapy: 22.1% (17/77 patients) - p=0.017 vs combination
- Azathioprine monotherapy: 23.7% (18/76 patients) - p=0.032 vs combination
Secondary Outcomes
Mucosal healing at week 16 showed: 1
- Combination therapy: 62.8% (49/78 patients)
- Infliximab monotherapy: 54.6% (42/77 patients) - p=0.295 vs combination
- Azathioprine monotherapy: 36.8% (28/76 patients) - p=0.001 vs combination
The combination therapy demonstrated statistically significant superiority over azathioprine monotherapy for mucosal healing, though the difference versus infliximab monotherapy did not reach statistical significance. 1
Important Clarification About Your Question
Your question contains a critical error: The UC-SUCCESS trial showed benefit of adding azathioprine to infliximab, not "no benefit." 1 There is no landmark trial showing no benefit of combination therapy with TNF-alpha antagonists and azathioprine in ulcerative colitis.
Current Guideline Recommendations Based on UC-SUCCESS
The 2020 AGA guidelines conditionally suggest combining TNF-α antagonists with thiopurines or methotrexate rather than biologic monotherapy in moderate-severe ulcerative colitis, based primarily on the UC-SUCCESS trial results. 2
However, the guidelines acknowledge this is a conditional recommendation with low-quality evidence because: 2
- The trial was terminated prematurely
- No maintenance phase data were completed
- Evidence for non-infliximab TNF antagonists is extrapolated (indirect evidence)
- Newer biologics may have lower immunogenicity than infliximab
Safety Considerations
Serious infections occurred in only 2 patients in UC-SUCCESS (one receiving infliximab monotherapy, one receiving azathioprine monotherapy), though combination therapy with anti-TNF agents and thiopurines generally increases risk of opportunistic infections and malignancy. 3, 1