LUCENT-1 and LUCENT-2UC · Induction and maintenance
Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis
D'Haens G, et al.
N Engl J Med 2023 · PMID 37379135 (PubMed, opens in a new tab) · doi 10.1056/NEJMoa2207940 (full paper, opens in a new tab)
| Endpoint | Mirikizumab | Placebo | Difference |
|---|---|---|---|
| LUCENT-1 induction, Clinical remission, week 12 · 300 mg IV every 4 weeks (primary endpoint) | 24.2% | 13.3% | P<0.001 |
| LUCENT-2 maintenance, Clinical remission, week 40 · 200 mg SC every 4 weeks (primary endpoint) | 49.9% | 25.1% | P<0.001 |
Source: D'Haens 2023, abstract. The abstract gives percentages only, not counts. In maintenance, placebo means withdrawal of mirikizumab after response to induction.
Structured abstract
BackgroundMirikizumab, an IL-23 p19 antibody, had shown efficacy in UC in a phase 2 trial; phase 3 trials were needed to confirm induction and maintenance benefit, including on bowel urgency.
MethodsTwo phase 3, randomised, double-blind, placebo-controlled trials: 12-week IV induction (3:1) and 40-week SC randomised-withdrawal maintenance (2:1). 1,281 patients. Primary endpoint: Clinical remission at week 12 (induction) and at week 40 of maintenance (week 52 overall).
ResultsPrimary result. Induction: 24.2% vs 13.3% (P<0.001). Maintenance: 49.9% vs 25.1% (P<0.001).
Take-homeMirikizumab, an IL-23 p19 antibody, induces and maintains remission in UC and improves bowel urgency.
| Patients | 1,281 |
|---|---|
| Population | Adults with moderately to severely active UC. 544 induction responders re-randomised in maintenance. Induction non-responders could receive open-label extended induction during the first 12 weeks of maintenance. |
| Comparison | Mirikizumab 300 mg IV every 4 weeks for 12 weeks vs placebo; responders randomised to 200 mg SC every 4 weeks vs placebo |
| Drugs | mirikizumab |
| Classes | Anti-IL-23 (p19) |
| Published | D'Haens G, et al. N Engl J Med 2023;388:2444–55. |
Key points
- All major secondary endpoints were met in both trials, including clinical response, endoscopic remission and improvement in bowel-movement urgency.
- Nasopharyngitis and arthralgia were more frequent with mirikizumab.
- Among 1217 mirikizumab-treated patients (all periods), 15 had an opportunistic infection (6 herpes zoster) and 8 had cancer (3 colorectal).
- LUCENT-3 extension (PMID 41777218): among week-52 remitters, 77.7% were in clinical remission at week 212 (observed cases).
Limitations
- Maintenance used randomised withdrawal of induction responders.
- No active comparator.
- The long-term extension figure quoted is an observed-case analysis of patients who stayed on treatment, which overstates durability.
Commentary
Why it matters. LUCENT made bowel urgency, one of the most disabling UC symptoms, a formal trial endpoint. It also offered open-label extended induction to patients without a response at week 12.
Related. Other IL-23 p19 antibodies in UC: risankizumab (INSPIRE and COMMAND, PMID 39037800) and guselkumab (QUASAR, PMID 39706209; ASTRO, PMID 41544637). The IL-12/23 antibody ustekinumab was tested in UNIFI (PMID 31553833).
Canada. Mirikizumab is marketed in Canada.
Journal club
Design
Two phase 3, randomised, double-blind, placebo-controlled trials: 12-week IV induction (3:1) and 40-week SC randomised-withdrawal maintenance (2:1). 1,281 patients.
Primary result. Induction: 24.2% vs 13.3% (P<0.001). Maintenance: 49.9% vs 25.1% (P<0.001).
Validity and applicability
- Maintenance used randomised withdrawal of induction responders.
- No active comparator.
- The long-term extension figure quoted is an observed-case analysis of patients who stayed on treatment, which overstates durability.
Where it sits now
Mirikizumab, an IL-23 p19 antibody, induces and maintains remission in UC and improves bowel urgency.
- 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
- Maintenance re-randomised only induction responders. How does that design affect the maintenance remission rate you would quote to a patient?
- Bowel urgency was a major secondary endpoint. How would you measure urgency in clinic, and does it change your choice of drug?
- With no active comparator, how would you place mirikizumab among the other IL-23 p19 antibodies?