True NorthUC · Induction and maintenance
Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis
Sandborn WJ, et al.
N Engl J Med 2021 · PMID 34587385 (PubMed, opens in a new tab) · doi 10.1056/NEJMoa2033617 (full paper, opens in a new tab)
| Endpoint | Ozanimod | Placebo | Difference |
|---|---|---|---|
| Clinical remission, Week 10 · induction (primary endpoint) | 18.4% | 6.0% | P<0.001 |
| Clinical response, Week 10 · induction | 47.8% | 25.9% | P<0.001 |
| Clinical remission, Week 52 · maintenance (primary endpoint) | 37.0% | 18.5% | P<0.001 |
| Clinical response, Week 52 · maintenance | 60.0% | 41.0% | P<0.001 |
Fewer than 1 in 5 patients reached remission at week 10, but about half responded.
Source: Sandborn 2021, abstract. Three-component Mayo score.
Structured abstract
BackgroundOzanimod is an oral sphingosine-1-phosphate receptor modulator that keeps lymphocytes out of the circulation. True North was its phase 3 induction and maintenance trial in moderately to severely active UC.
MethodsPhase 3, multicentre, randomised, double-blind, placebo-controlled: 10-week induction and randomised-withdrawal maintenance to week 52. 645 patients. Primary endpoint: Clinical remission by three-component Mayo score at week 10 (induction) and week 52 (maintenance, in week-10 responders).
ResultsPrimary result. Induction: 18.4% vs 6.0% (P<0.001). Maintenance: 37.0% vs 18.5% (P<0.001).
Take-homeOzanimod, a once-daily oral S1P receptor modulator, induces and maintains remission in UC with a low serious-infection rate.
| Patients | 645 |
|---|---|
| Population | Moderately to severely active UC. Induction cohort 1: 645 randomised (double-blind); cohort 2: 367 open-label ozanimod. 457 week-10 responders entered randomised maintenance. |
| Comparison | Ozanimod 0.92 mg (ozanimod hydrochloride 1 mg) once daily vs placebo |
| Drugs | ozanimod |
| Classes | S1P receptor modulator |
| Published | Sandborn WJ, et al. N Engl J Med 2021;385:1280–91. |
Key points
- Clinical response: 47.8% vs 25.9% in induction and 60.0% vs 41.0% in maintenance (both P<0.001).
- All other key secondary clinical, endoscopic and histologic endpoints were met in both periods.
- Infections were similar to placebo in induction and more frequent in maintenance; serious infection occurred in less than 2% of each group over 52 weeks.
- Elevated liver aminotransferases were more common with ozanimod.
Limitations
- Modest induction remission rate (18.4%).
- Maintenance used randomised withdrawal of responders.
- No active comparator.
Commentary
Context. True North introduced the S1P receptor modulators to UC. They trap lymphocytes in lymph nodes and are taken by mouth. Class precautions (heart rate and conduction effects at the start, macular oedema, liver enzymes, infection and drug interactions) mean baseline screening is needed; follow the Canadian product monograph.
Related. Etrasimod (ELEVATE UC 52 and UC 12, PMID 36871574) is a second S1P modulator tested with a treat-through design.
Canada. Ozanimod is marketed in Canada.
Journal club
Design
Phase 3, multicentre, randomised, double-blind, placebo-controlled: 10-week induction and randomised-withdrawal maintenance to week 52. 645 patients.
Primary result. Induction: 18.4% vs 6.0% (P<0.001). Maintenance: 37.0% vs 18.5% (P<0.001).
Validity and applicability
- Modest induction remission rate (18.4%).
- Maintenance used randomised withdrawal of responders.
- No active comparator.
Where it sits now
Ozanimod, a once-daily oral S1P receptor modulator, induces and maintains remission in UC with a low serious-infection rate.
- 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 18.4%. Where would you place a modest-efficacy oral drug for a patient who wants to avoid injections?
- Maintenance re-randomised week-10 responders. How does that design raise maintenance remission compared with a treat-through trial?
- Which baseline checks would you arrange before starting ozanimod, and why?