ULTRA 2UC · Induction and maintenance
Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis
Sandborn WJ, et al.
Gastroenterology 2012 · PMID 22062358 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2011.10.032 (full paper, opens in a new tab)
| Endpoint | Adalimumab | Placebo | Difference |
|---|---|---|---|
| Clinical remission, all patients, Week 8 (primary endpoint) | 16.5% | 9.3% | P=0.019 |
| Anti-TNF-naive, Week 8 · subgroup | 21.3% | 11% | P=0.017 |
| Prior anti-TNF, Week 8 · subgroup | 9.2% | 6.9% | P=0.559 (not significant) |
| Clinical remission, all patients, Week 52 (primary endpoint) | 17.3% | 8.5% | P=0.004 |
| Anti-TNF-naive, Week 52 · subgroup | 22% | 12.4% | P=0.029 |
| Prior anti-TNF, Week 52 · subgroup | 10.2% | 3% | P=0.039 |
After prior anti-TNF exposure, adalimumab did not beat placebo at week 8.
Source: Sandborn 2012, abstract. Randomisation was stratified by prior anti-TNF exposure; subgroup percentages are printed as in the abstract, which does not give subgroup sizes.
Structured abstract
BackgroundInfliximab was established in UC, but adalimumab, a subcutaneous anti-TNF, had not been studied as maintenance therapy for UC in a controlled, double-blind trial.
MethodsRandomised, double-blind, placebo-controlled 52-week trial (treat-through), stratified by prior anti-TNF exposure. 494 patients. Primary endpoint: Clinical remission at week 8 and at week 52.
ResultsPrimary result. Week 8: 16.5% vs 9.3% (P=0.019). Week 52: 17.3% vs 8.5% (P=0.004).
Take-homeAdalimumab works in UC, but absolute remission rates are modest, especially after prior anti-TNF failure.
| Patients | 494 |
|---|---|
| Population | Moderate to severe UC on concurrent oral corticosteroids or immunosuppressants; both anti-TNF-naive and anti-TNF-exposed patients |
| Comparison | Adalimumab SC 160 mg week 0, 80 mg week 2, then 40 mg every other week, vs placebo |
| Drugs | adalimumab |
| Classes | Anti-TNF |
| Published | Sandborn WJ, et al. Gastroenterology 2012;142:257–65. |
Key points
- Anti-TNF-naive: remission 21.3% vs 11% at week 8 (P=0.017) and 22% vs 12.4% at week 52 (P=0.029).
- Prior anti-TNF: remission 9.2% vs 6.9% at week 8 (P=0.559, not significant) and 10.2% vs 3% at week 52 (P=0.039).
- Serious adverse events occurred in 12% of both groups; serious infections in 1.6% (adalimumab) vs 1.9% (placebo).
- One squamous cell carcinoma and one gastric cancer occurred in the adalimumab group.
Limitations
- Low absolute remission rates and a modest gain over placebo.
- Treat-through design, so maintenance rates include patients who never responded to induction.
- Underpowered for the anti-TNF-exposed subgroup.
Commentary
Context. ULTRA 2 supported approval of subcutaneous adalimumab for UC. Its modest effect size became important when VARSITY (PMID 31553834) showed vedolizumab was superior to adalimumab for clinical remission and endoscopic improvement at week 52.
Dose. SERENE-UC (PMID 35227777) tested higher induction and maintenance doses. Higher induction dosing did not improve week-8 remission, and weekly maintenance did not significantly beat every-other-week dosing on the primary endpoint.
Canada. Several adalimumab biosimilars are marketed in Canada.
Journal club
Design
Randomised, double-blind, placebo-controlled 52-week trial (treat-through), stratified by prior anti-TNF exposure. 494 patients.
Primary result. Week 8: 16.5% vs 9.3% (P=0.019). Week 52: 17.3% vs 8.5% (P=0.004).
Validity and applicability
- Low absolute remission rates and a modest gain over placebo.
- Treat-through design, so maintenance rates include patients who never responded to induction.
- Underpowered for the anti-TNF-exposed subgroup.
Where it sits now
Adalimumab works in UC, but absolute remission rates are modest, especially after prior anti-TNF failure.
- 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
- Remission at week 52 was 17.3% vs 8.5%. How would you present a 9-point absolute gain to a patient choosing between drugs?
- Patients with prior anti-TNF exposure had no significant week-8 benefit. Would you start adalimumab after infliximab failure, and what would sway you?
- ULTRA 2 used a treat-through design. How does that make its maintenance rates look lower than those of withdrawal trials such as GEMINI 1 or UNIFI?