ACTIVEUC · Acute severe colitis
Top-down infliximab plus azathioprine versus azathioprine alone in patients with acute severe ulcerative colitis responsive to intravenous steroids: a parallel, open-label randomised controlled trial, the ACTIVE trial
Amiot A, et al.
Gut 2025 · PMID 39586616 (PubMed, opens in a new tab) · doi 10.1136/gutjnl-2024-333281 (full paper, opens in a new tab)
| Endpoint | Combination | Azathioprine | Difference |
|---|---|---|---|
| Treatment failure, Week 52 · composite; lower is better (primary endpoint) | 53.3% (16/30) | 81.5% (22/27) | P=0.03 |
Denominators of 30 and 27 are smaller than the 32 randomised to each arm.
Source: Amiot 2025, abstract. Counts as printed (27 and 30 patients analysed; 32 randomised per arm); the authors' intention-to-treat analysis used multiple imputation for missing data.
Structured abstract
BackgroundFor thiopurine- and biologic-naive patients whose acute severe UC responds to IV steroids, it was unknown which maintenance therapy works best; azathioprine alone was the traditional choice.
MethodsMulticentre, parallel-group, open-label randomised controlled trial (23 French centres). 64 patients. Primary endpoint: Treatment failure at week 52: no steroid-free clinical remission, no endoscopic response, prohibited rescue treatment, severe adverse event stopping treatment, colectomy or death.
ResultsPrimary result. Treatment failure 81.5% (22/27) with azathioprine alone vs 53.3% (16/30) with infliximab plus azathioprine; P=0.03.
Take-homeAfter a steroid-responsive episode of acute severe UC in a thiopurine- and biologic-naive patient, starting infliximab plus azathioprine reduced 1-year treatment failure compared with azathioprine alone.
| Patients | 64 |
|---|---|
| Population | Thiopurine- and biologic-naive adults admitted with acute severe UC who responded to IV steroids (mean Lichtiger score 13.5; median CRP 29.0 mg/L). |
| Comparison | Infliximab plus azathioprine with a 7-day steroid taper (n=32) vs azathioprine with a conventional standardised steroid taper (n=32) |
| Drugs | infliximab, azathioprine |
| Classes | Anti-TNF, Thiopurine |
| Published | Amiot A, et al. Gut 2025;74:197–205. |
Key points
- Nearly 4 in 5 patients started on azathioprine alone after a steroid-responsive attack had failed by 1 year.
- 29 severe adverse events, including 13 disease exacerbations and 6 severe infections, with no difference between arms.
- Intention-to-treat analysis with multiple imputation for missing data.
Limitations
- Small and open-label; the composite endpoint mixes clinical, endoscopic and safety outcomes.
- Steroid tapering differed between arms (7 days vs conventional), so part of the effect may reflect the strategy rather than the drug alone.
- Did not test newer advanced therapies as maintenance after acute severe UC.
Commentary
Most acute severe UC trials ask what to do when IV steroids fail (CONSTRUCT, CYSIF). ACTIVE asks the next question: what maintenance should follow when steroids work? The traditional answer, a thiopurine alone, failed in most patients within a year.
How to use it: an admission with acute severe UC marks aggressive disease. For a patient who responds to IV steroids and has not had a thiopurine or biologic, plan an advanced therapy for maintenance rather than relying on a thiopurine alone. Infliximab with azathioprine is the regimen tested here; other advanced therapies are often used but were not studied in this trial.
Journal club
Design
Multicentre, parallel-group, open-label randomised controlled trial (23 French centres). 64 patients.
Primary result. Treatment failure 81.5% (22/27) with azathioprine alone vs 53.3% (16/30) with infliximab plus azathioprine; P=0.03.
Validity and applicability
- Small and open-label; the composite endpoint mixes clinical, endoscopic and safety outcomes.
- Steroid tapering differed between arms (7 days vs conventional), so part of the effect may reflect the strategy rather than the drug alone.
- Did not test newer advanced therapies as maintenance after acute severe UC.
Where it sits now
After a steroid-responsive episode of acute severe UC in a thiopurine- and biologic-naive patient, starting infliximab plus azathioprine reduced 1-year treatment failure compared with azathioprine alone.
- CONSTRUCT (2016): In steroid-refractory acute severe UC, infliximab and ciclosporin are equally effective rescue therapies; choose by local experience, patient factors and the maintenance plan.
- CYSIF (2012): Ciclosporin and infliximab perform similarly as rescue therapy for steroid-refractory acute severe UC, in the short and long term.
- PREDICT-UC (2024): In steroid-refractory acute severe UC, a 10 mg/kg first infliximab dose or an accelerated schedule was not better than standard 5 mg/kg dosing.
- TACOS (2024): Adding tofacitinib to IV steroids improved day-7 response in acute severe UC in one small single-centre trial; promising, but not yet standard care.
Questions for discussion
- The abstract calls the effect a 'risk ratio' of 3.85 for failure rates of 81.5% and 53.3%. Which measure do those numbers fit, and why does the choice of measure matter when outcomes are common?
- The infliximab arm also had a 7-day steroid taper. How would you separate the effect of the drug from the effect of the tapering strategy?
- Would you extend this result to vedolizumab, ustekinumab or a JAK inhibitor as maintenance after a steroid-responsive episode of acute severe UC?