UNIFIMust knowUC · Induction and maintenance
Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis
Sands BE, et al.
N Engl J Med 2019 · PMID 31553833 (PubMed, opens in a new tab) · doi 10.1056/NEJMoa1900750 (full paper, opens in a new tab)
| Endpoint | 130 mg IV | About 6 mg/kg IV | 90 mg SC every 12 weeks | 90 mg SC every 8 weeks | Placebo | Difference |
|---|---|---|---|---|---|---|
| Clinical remission, Week 8 · induction (primary endpoint) | 15.6% | 15.5% | not in this comparison | not in this comparison | 5.3% | P<0.001 for both doses vs placebo |
| Clinical remission, Week 44 · re-randomised responders (primary endpoint) | not in this comparison | not in this comparison | 38.4% | 43.8% | 24.0% | Every 12 weeks P=0.002; every 8 weeks P<0.001 vs placebo |
About 1 in 6 patients was in remission 8 weeks after one IV dose; maintenance results apply only to those who responded.
Source: Sands 2019, abstract. The induction and maintenance placebo groups are different patients.
Structured abstract
BackgroundUstekinumab, an antibody to the p40 subunit shared by IL-12 and IL-23, was approved for Crohn's disease, but its efficacy as induction and maintenance therapy in UC was unknown.
MethodsPhase 3, randomised, double-blind, placebo-controlled: 8-week IV induction and 44-week randomised-withdrawal SC maintenance. 961 patients. Primary endpoint: Clinical remission (total Mayo ≤2, no subscore >1) at week 8 (induction) and week 44 (maintenance).
ResultsPrimary result. Week 8: 15.6% (130 mg) and 15.5% (6 mg/kg) vs 5.3% (P<0.001 for both). Week 44: 38.4% (every 12 weeks) and 43.8% (every 8 weeks) vs 24.0% (P=0.002 and P<0.001).
Take-homeUstekinumab, an IL-12/23 antibody, induces and maintains remission in UC with a reassuring safety profile.
| Patients | 961 |
|---|---|
| Population | Moderate to severe UC. Maintenance: 523 responders to IV ustekinumab induction re-randomised (172 every 12 weeks, 176 every 8 weeks, 175 placebo). |
| Comparison | Ustekinumab IV 130 mg or about 6 mg/kg (weight-range dosing) vs placebo; responders randomised to 90 mg SC every 12 weeks, every 8 weeks, or placebo |
| Drugs | ustekinumab |
| Classes | Anti-IL-12/23 |
| Published | Sands BE, et al. N Engl J Med 2019;381:1201–14. |
Key points
- Serious adverse events were similar to placebo.
- Through 52 weeks: 2 deaths and 7 cancers among 825 ustekinumab-treated patients vs no deaths and 1 cancer among 319 placebo patients.
- The weight-based (about 6 mg/kg) single IV induction dose became the standard.
Limitations
- Modest induction remission rates (about 15%).
- Maintenance used randomised withdrawal of induction responders.
- No active comparator.
Commentary
Why it matters. UNIFI added a new mechanism (IL-12/23 blockade) for UC with a convenient schedule: one IV dose, then injections every 8 or 12 weeks. Its safety record from psoriasis and Crohn’s disease made it attractive for older patients and those with comorbidities.
What came after. Selective IL-23 p19 antibodies followed: mirikizumab (LUCENT, PMID 37379135), risankizumab (INSPIRE and COMMAND, PMID 39037800) and guselkumab (QUASAR, PMID 39706209).
Canada. Ustekinumab biosimilars are now marketed in Canada.
Journal club
Design
Phase 3, randomised, double-blind, placebo-controlled: 8-week IV induction and 44-week randomised-withdrawal SC maintenance. 961 patients.
Primary result. Week 8: 15.6% (130 mg) and 15.5% (6 mg/kg) vs 5.3% (P<0.001 for both). Week 44: 38.4% (every 12 weeks) and 43.8% (every 8 weeks) vs 24.0% (P=0.002 and P<0.001).
Validity and applicability
- Modest induction remission rates (about 15%).
- Maintenance used randomised withdrawal of induction responders.
- No active comparator.
Where it sits now
Ustekinumab, an IL-12/23 antibody, induces and maintains remission in UC with a reassuring safety profile.
- 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
- Induction remission was about 15% at week 8. Would you judge ustekinumab at week 8, or wait longer before switching?
- Every-8-week dosing gave numerically more remission than every 12 weeks. How would you choose the interval?
- Maintenance re-randomised responders. How does that affect comparison with a treat-through trial such as ULTRA 2?