VIVID-1CD · Induction and maintenance
Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study
Ferrante M, et al.
Lancet 2024 · PMID 39581202 (PubMed, opens in a new tab) · doi 10.1016/S0140-6736(24)01762-8 (full paper, opens in a new tab)
| Endpoint | Mirikizumab | Placebo | Difference |
|---|---|---|---|
| Endoscopic-response composite, Week 12 response + week 52 endoscopic response (primary endpoint) | 38.0% (220/579) | 9.0% (18/199) | Difference 99.5% CI 20.6–36.8; P<0.0001 |
| CDAI-remission composite, Week 12 response + week 52 CDAI remission (primary endpoint) | 45.4% (263/579) | 19.6% (39/199) | Difference 99.5% CI 15.9–35.6; P<0.0001 |
Composites spanning weeks 12 and 52 set a stricter bar than a single time point, so these rates cannot be compared directly with other trials.
Source: Ferrante 2024, abstract. The abstract prints the 99.5% CI of the adjusted difference but not the point estimate, and does not report the ustekinumab arm for these endpoints.
Structured abstract
BackgroundMirikizumab, an IL-23 p19 antibody, was already effective in UC. VIVID-1 tested it in Crohn's disease against placebo, with ustekinumab as an active reference arm, in a treat-through design.
MethodsPhase 3, randomised (6:3:2), double-blind, double-dummy, placebo-controlled and active-controlled treat-through study (324 sites, 33 countries). 1,150 patients. Primary endpoint: Two composite co-primary endpoints vs placebo: (1) patient-reported-outcome clinical response at week 12 plus endoscopic response at week 52; (2) patient-reported-outcome clinical response at week 12 plus CDAI clinical remission at week 52.
ResultsPrimary result. Endoscopic-response composite 38.0% (220/579) vs 9.0% (18/199) (99.5% CI 20.6–36.8; P<0.0001). CDAI-remission composite 45.4% (263/579) vs 19.6% (39/199) (99.5% CI 15.9–35.6; P<0.0001).
Take-homeMirikizumab, an IL-23 p19 inhibitor, induces and maintains clinical and endoscopic response in Crohn's disease, including after biologic failure.
| Patients | 1,150 |
|---|---|
| Population | Adults with moderately-to-severely active Crohn's disease and inadequate response, loss of response or intolerance to at least one approved biologic or conventional therapy. 1150 randomised and treated; 1065 in the efficacy population. |
| Comparison | Mirikizumab vs ustekinumab vs placebo |
| Drugs | mirikizumab, ustekinumab |
| Classes | Anti-IL-23 p19, Anti-IL-12/23 |
| Published | Ferrante M, et al. Lancet 2024;404:2423–36. |
Key points
- Mirikizumab 900 mg IV at weeks 0, 4 and 8, then 300 mg SC every 4 weeks; ustekinumab about 6 mg/kg IV, then 90 mg SC every 8 weeks; to week 52.
- Serious adverse events: 10.3% (65/630) mirikizumab, 10.7% (33/309) ustekinumab, 17.1% (36/211) placebo.
- Three deaths (one ustekinumab, two placebo), none considered related to study drug. COVID-19 was the most common adverse event.
- Ustekinumab was an active reference arm; the mirikizumab–ustekinumab comparisons were secondary endpoints and are not reported in the abstract (see the full paper).
- Treat-through design: patients stayed on their assigned drug from induction into maintenance, unlike withdrawal designs.
Limitations
- Composite co-primary endpoints across weeks 12 and 52 are hard to compare with other trials.
- The trial was not designed primarily as a head-to-head comparison with ustekinumab.
- Industry funded (Eli Lilly).
Commentary
VIVID-1 extended mirikizumab, already used for ulcerative colitis, to Crohn’s disease. Its treat-through design with a placebo arm to week 52 is more demanding than older withdrawal designs, which partly explains the very low placebo composite rates.
Later evidence. In the VIVID-2 open-label extension (430 patients in the efficacy population), 73.4% were in CDAI remission and 37.9% in endoscopic remission at week 104 (modified non-responder imputation). Of patients without an endoscopic response at week 52, who were reinduced with 900 mg IV at weeks 0, 4 and 8, 30.9% reached endoscopic response at week 104 (Sands BE, et al. Clin Gastroenterol Hepatol 2026;24:2512–23; PMID 41794217). These uncontrolled data support durability and a role for IV reinduction.
For the cleanest head-to-head evidence of an IL-23 p19 inhibitor against ustekinumab, see SEQUENCE.
Journal club
Design
Phase 3, randomised (6:3:2), double-blind, double-dummy, placebo-controlled and active-controlled treat-through study (324 sites, 33 countries). 1,150 patients.
Primary result. Endoscopic-response composite 38.0% (220/579) vs 9.0% (18/199) (99.5% CI 20.6–36.8; P<0.0001). CDAI-remission composite 45.4% (263/579) vs 19.6% (39/199) (99.5% CI 15.9–35.6; P<0.0001).
Validity and applicability
- Composite co-primary endpoints across weeks 12 and 52 are hard to compare with other trials.
- The trial was not designed primarily as a head-to-head comparison with ustekinumab.
- Industry funded (Eli Lilly).
Where it sits now
Mirikizumab, an IL-23 p19 inhibitor, induces and maintains clinical and endoscopic response in Crohn's disease, including after biologic failure.
- SEQUENCE (2024): After anti-TNF failure, risankizumab beats ustekinumab for endoscopic remission, so an IL-23 p19 inhibitor is the stronger second-line choice of the two.
- RELIEVE UCCD (CD) (2026): Duvakitug, an anti-TL1A antibody, gave a dose-related endoscopic response signal in Crohn's disease in phase 2b; phase 3 trials will decide whether TL1A becomes a new Crohn's disease target.
- DIVERSITY (2025): Filgotinib failed its week-10 induction endpoints in Crohn's disease, unlike upadacitinib in its own phase 3 trials, so JAK inhibitors should not be assumed to work equally well in Crohn's disease.
- GALAXI-2 and GALAXI-3 (2025): IV guselkumab induction followed by SC maintenance is effective in Crohn's disease and outperformed ustekinumab at week 48 on several endpoints.
Questions for discussion
- The co-primary endpoints combined a week-12 symptom response with a week-52 outcome. How does a composite like this compare with separate induction and maintenance endpoints?
- Ustekinumab was included, but the trial was not designed as a head-to-head. What can and can't you conclude about mirikizumab versus ustekinumab?
- In a treat-through design, patients stayed on their drug. How does that change the meaning of week-52 rates compared with randomised withdrawal?