UC-SUCCESSMust knowUC · Treatment strategy
Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis
Panaccione R, et al.
Gastroenterology 2014 · PMID 24512909 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2013.10.052 (full paper, opens in a new tab)
| Endpoint | Combination | Infliximab | Azathioprine | Difference |
|---|---|---|---|---|
| Corticosteroid-free remission, Week 16 (primary endpoint) | 39.7% (31/78) | 22.1% (17/77) | 23.7% (18/76) | Combination vs infliximab P=0.017; vs azathioprine P=0.032 |
| Mucosal healing, Week 16 | 62.8% (49/78) | 54.6% (42/77) | 36.8% (28/76) | Combination vs infliximab P=0.295; vs azathioprine P=0.001 |
Infliximab alone and azathioprine alone gave similar steroid-free remission at 16 weeks.
Source: Panaccione 2014, abstract. The trial stopped before reaching its enrolment target.
Structured abstract
BackgroundSONIC showed that infliximab plus azathioprine outperformed either drug alone in Crohn's disease. The same comparison had not been made in ulcerative colitis.
MethodsRandomised, double-blind, 16-week trial with matching placebo infusions and capsules; stopped before reaching its enrolment target. 239 patients. Primary endpoint: Corticosteroid-free clinical remission at week 16 (total Mayo score ≤2 with no subscore above 1, off corticosteroids).
ResultsPrimary result. Combination 39.7% (31/78) vs infliximab alone 22.1% (17/77), P=0.017, and vs azathioprine alone 23.7% (18/76), P=0.032
Take-homeWhen starting infliximab in anti-TNF-naive UC, adding azathioprine improves steroid-free remission at 16 weeks (40% vs 22%).
| Patients | 239 |
|---|---|
| Population | Anti-TNF-naive adults with moderate to severe UC (Mayo 6–12) and an inadequate response to corticosteroids; thiopurine-naive or off a thiopurine for at least 3 months (per the trial registration). 239 in the efficacy analyses; the primary-endpoint denominators total 231. |
| Comparison | Infliximab 5 mg/kg (weeks 0, 2, 6, 14) plus azathioprine 2.5 mg/kg/day vs infliximab alone vs azathioprine alone |
| Drugs | infliximab, azathioprine |
| Classes | Anti-TNF, Thiopurine |
| Published | Panaccione R, et al. Gastroenterology 2014;146:392–400. |
Key points
- Mucosal healing at week 16: 62.8% (49/78) with combination vs 54.6% (42/77) with infliximab alone (P=0.295, not significant) and 36.8% (28/76) with azathioprine alone (P=0.001).
- Infliximab alone and azathioprine alone gave similar steroid-free remission at 16 weeks (22.1% vs 23.7%).
- Serious infections were uncommon: 2 patients (1 on infliximab, 1 on azathioprine).
- The UC counterpart of SONIC in Crohn's disease (PMID 20393175), which showed the same combination advantage.
Limitations
- Terminated early, below its enrolment target, so secondary comparisons are underpowered.
- Only 16 weeks of follow-up: no long-term efficacy or safety data (for example infection or lymphoma risk with combination therapy).
- The mucosal-healing difference between combination and infliximab alone was not significant.
Commentary
Why it matters. UC-SUCCESS is the main randomised evidence for combination therapy in UC. Together with SONIC in Crohn’s disease (PMID 20393175), it is the basis for offering a thiopurine with infliximab when starting anti-TNF therapy.
Using it in practice. The benefit has to be weighed against thiopurine toxicity and the long-term risks of combined immunosuppression, which this 16-week trial could not measure. Many clinicians individualise: combination therapy for most patients starting infliximab, with more caution in groups at higher thiopurine risk.
Journal club
Design
Randomised, double-blind, 16-week trial with matching placebo infusions and capsules; stopped before reaching its enrolment target. 239 patients.
Primary result. Combination 39.7% (31/78) vs infliximab alone 22.1% (17/77), P=0.017, and vs azathioprine alone 23.7% (18/76), P=0.032
Validity and applicability
- Terminated early, below its enrolment target, so secondary comparisons are underpowered.
- Only 16 weeks of follow-up: no long-term efficacy or safety data (for example infection or lymphoma risk with combination therapy).
- The mucosal-healing difference between combination and infliximab alone was not significant.
Where it sits now
When starting infliximab in anti-TNF-naive UC, adding azathioprine improves steroid-free remission at 16 weeks (40% vs 22%).
- Upadacitinib plus vedolizumab induction (2026): Adding 8 weeks of upadacitinib to vedolizumab induction improved early endoscopic remission over vedolizumab alone, but this small open-label trial is hypothesis-generating.
- VEGA (2023): Combining an anti-TNF with an IL-23 antibody for induction outperformed golimumab alone but did not clearly separate from guselkumab alone; this phase 2 signal needs phase 3 confirmation.
Questions for discussion
- The trial stopped early and lasted only 16 weeks. How confident are you that the combination benefit holds at 1 year?
- Mucosal healing did not differ significantly between combination and infliximab alone. Which endpoint would you emphasise when advising a patient?
- Would you add a thiopurine to adalimumab, vedolizumab or ustekinumab on the strength of SONIC and UC-SUCCESS? What evidence would you want?