ACT 1 and ACT 2Must knowUC · Induction and maintenance
Infliximab for induction and maintenance therapy for ulcerative colitis
Rutgeerts P, et al.
N Engl J Med 2005 · PMID 16339095 (PubMed, opens in a new tab) · doi 10.1056/NEJMoa050516 (full paper, opens in a new tab)
| Endpoint | 5 mg/kg | 10 mg/kg | Placebo | Difference |
|---|---|---|---|---|
| Clinical response, Week 8 · ACT 1 (primary endpoint) | 69% | 61% | 37% | P<0.001 for each dose vs placebo |
| Clinical response, Week 8 · ACT 2 (primary endpoint) | 64% | 69% | 29% | P<0.001 for each dose vs placebo |
| Clinical response, Week 54 · ACT 1 | 45% | 44% | 20% | P<0.001 for each dose vs placebo |
Doubling the dose added no consistent benefit, so 5 mg/kg became the standard.
Source: Rutgeerts 2005, abstract. The abstract gives no counts or confidence intervals.
Structured abstract
BackgroundInfliximab was established in Crohn's disease, but whether an anti-TNF antibody could induce and maintain response in moderate to severe UC was unknown.
MethodsTwo randomised, double-blind, placebo-controlled trials (treat-through: patients stayed on their assigned arm). 728 patients. Primary endpoint: Clinical response at week 8 (Mayo score down ≥3 points and ≥30%, with rectal-bleeding subscore down ≥1 or an absolute subscore of 0–1).
ResultsPrimary result. ACT 1: 69% (5 mg/kg) and 61% (10 mg/kg) vs 37% with placebo. ACT 2: 64% and 69% vs 29%. P<0.001 for every comparison with placebo.
Take-homeInfliximab 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks, induces and maintains response in moderate to severe UC; doubling the dose gave no consistent added benefit.
| Patients | 728 |
|---|---|
| Population | Moderate to severe active UC despite concurrent medications; 364 patients in each trial. Treatment through week 46 (ACT 1, follow-up 54 weeks) or week 22 (ACT 2, follow-up 30 weeks). |
| Comparison | Infliximab IV 5 mg/kg or 10 mg/kg at weeks 0, 2 and 6, then every 8 weeks, vs placebo |
| Drugs | infliximab |
| Classes | Anti-TNF |
| Published | Rutgeerts P, et al. N Engl J Med 2005;353:2462–76. |
Key points
- Response was durable: infliximab beat placebo for clinical response at week 30 in both trials (P≤0.002 for all comparisons).
- ACT 1, week 54 clinical response: 45% (5 mg/kg) and 44% (10 mg/kg) vs 20% with placebo (P<0.001 for both).
- 10 mg/kg gave no consistent advantage over 5 mg/kg, which became the standard dose.
- These were the trials that established the first biologic for moderate to severe UC.
Limitations
- Published in 2005, before endoscopic, histologic and treat-to-target goals were standard.
- The primary endpoint was clinical response, a lower bar than remission.
- Treat-through design: maintenance results include induction non-responders, unlike later randomised-withdrawal trials, so they are not directly comparable.
Commentary
ACT 1 and 2 are older than the 15-year window of this library but are included because almost every later UC trial was built on their design and endpoints (Mayo score response and remission at weeks 8, 30 and 54).
What came after. UC-SUCCESS (PMID 24512909) showed that adding azathioprine to infliximab improved steroid-free remission at week 16 in anti-TNF-naive patients. In acute severe UC, CYSIF (PMID 23063316) and CONSTRUCT (PMID 27595142) found infliximab and ciclosporin to be similarly effective rescue therapies, and PREDICT-UC (PMID 39236736) found no benefit from a 10 mg/kg first dose over 5 mg/kg in steroid-refractory disease.
Teaching point. The 5 mg/kg dose and the 0, 2, 6-week induction schedule used in practice today come directly from these trials.
Journal club
Design
Two randomised, double-blind, placebo-controlled trials (treat-through: patients stayed on their assigned arm). 728 patients.
Primary result. ACT 1: 69% (5 mg/kg) and 61% (10 mg/kg) vs 37% with placebo. ACT 2: 64% and 69% vs 29%. P<0.001 for every comparison with placebo.
Validity and applicability
- Published in 2005, before endoscopic, histologic and treat-to-target goals were standard.
- The primary endpoint was clinical response, a lower bar than remission.
- Treat-through design: maintenance results include induction non-responders, unlike later randomised-withdrawal trials, so they are not directly comparable.
Where it sits now
Infliximab 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks, induces and maintains response in moderate to severe UC; doubling the dose gave no consistent added benefit.
- ASTRO (2026): Guselkumab can be started with subcutaneous 400 mg injections instead of IV infusions, with clear benefit over placebo by week 12.
- RELIEVE UCCD (UC) (2026): Duvakitug, an anti-TL1A antibody, showed a dose-related remission signal in UC in phase 2b; phase 3 trials will decide its place.
- QUASAR (2025): Guselkumab induces and maintains remission in UC, and the follow-up ASTRO trial showed induction can be given subcutaneously.
- TUSCANY-2 (2025): Afimkibart missed its phase 2b primary endpoint (total Mayo remission), although remission by the modified Mayo score favoured it; anti-TL1A therapy still needs phase 3 proof.
Questions for discussion
- Week-54 response was about 45% in a treat-through design. How would that compare with a randomised-withdrawal trial that re-randomises only week-8 responders?
- The primary endpoint was clinical response, not remission or mucosal healing. What would you want to see before using these trials to set treatment targets today?
- 10 mg/kg gave no consistent advantage at a group level. Which patients might still need higher dosing, and how would you identify them now?