GALAXI-2 and GALAXI-3CD · Induction and maintenance
Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn's disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials
Panaccione R, et al.
Lancet 2025 · PMID 40684778 (PubMed, opens in a new tab) · doi 10.1016/S0140-6736(25)00681-6 (full paper, opens in a new tab)
| Endpoint | 200 mg | 100 mg | Placebo | Difference |
|---|---|---|---|---|
| Response + clinical remission, GALAXI-2 · weeks 12 and 48 (primary endpoint) | 55% (80/146) | 49% (70/143) | 12% (9/76) | Differences 43% (95% CI 32–54) and 38% (27–49); P<0.0001 |
| Response + clinical remission, GALAXI-3 · weeks 12 and 48 (primary endpoint) | 48% (72/150) | 47% (67/143) | 13% (9/72) | Differences 35% (95% CI 24–46) and 34% (23–45); P<0.0001 |
| Response + endoscopic response, GALAXI-2 · weeks 12 and 48 (primary endpoint) | 38% | 39% | 5% | Differences 33% (95% CI 24–42) and 34% (24–43); P<0.0001 |
| Response + endoscopic response, GALAXI-3 · weeks 12 and 48 (primary endpoint) | 36% | 34% | 6% | Differences 31% (95% CI 21–40) and 28% (19–37); P<0.0001 |
A composite needs response at week 12 and the outcome at week 48, so it counts slow responders and later loss of response as failures.
Source: Panaccione 2025, abstract (primary analysis population). Differences are adjusted, each guselkumab regimen vs placebo; the abstract gives denominators only for the response-plus-remission endpoint, so counts are shown only there. Comparisons with ustekinumab were secondary and are not shown.
Structured abstract
BackgroundGuselkumab, an IL-23 p19 antibody, was effective in UC; these trials tested IV induction and SC maintenance in Crohn's disease against both placebo and ustekinumab.
MethodsTwo identically designed phase 3, randomised (2:2:2:1), double-blind, triple-dummy, treat-through trials with placebo and active (ustekinumab) comparators (257 sites, 40 countries). 1,048 patients. Primary endpoint: Composite co-primary endpoints vs placebo: clinical response at week 12 plus clinical remission at week 48; and clinical response at week 12 plus endoscopic response at week 48.
ResultsPrimary result. Response plus remission, GALAXI-2: 55% (200 mg) and 49% (100 mg) vs 12% placebo; adjusted differences 43% (95% CI 32–54) and 38% (27–49); P<0.0001. GALAXI-3: 48% and 47% vs 13%; 35% (24–46) and 34% (23–45); P<0.0001.
Take-homeIV guselkumab induction followed by SC maintenance is effective in Crohn's disease and outperformed ustekinumab at week 48 on several endpoints.
| Patients | 1,048 |
|---|---|
| Population | Adults with moderately to severely active Crohn's disease of at least 3 months' duration. Primary analysis population 1021 (508 in GALAXI-2, 513 in GALAXI-3). |
| Comparison | Guselkumab (two maintenance doses) vs ustekinumab vs placebo |
| Drugs | guselkumab, ustekinumab |
| Classes | Anti-IL-23 p19, Anti-IL-12/23 |
| Published | Panaccione R, et al. Lancet 2025;406:358–75. |
Key points
- Guselkumab 200 mg IV at weeks 0, 4 and 8, then 200 mg SC every 4 weeks or 100 mg SC every 8 weeks; ustekinumab about 6 mg/kg IV, then 90 mg SC every 8 weeks.
- Response plus endoscopic response, GALAXI-2: 38% and 39% vs 5% (differences 33% [24–42] and 34% [24–43]). GALAXI-3: 36% and 34% vs 6% (31% [21–40] and 28% [19–37]). P<0.0001 for all.
- The authors report superiority of guselkumab over ustekinumab at week 48 across multiple endpoints (secondary comparisons; numbers in the full paper).
- Serious adverse events: 7% guselkumab 200 mg, 11% guselkumab 100 mg, 12% ustekinumab, 15% placebo. No deaths.
- Treat-through design: patients stayed on their randomised regimen regardless of week 12 response (placebo non-responders got masked ustekinumab rescue).
Limitations
- Head-to-head comparisons with ustekinumab were secondary endpoints.
- The primary analysis population was restricted to patients meeting SES-CD eligibility criteria added in a protocol amendment.
- Industry funded (Johnson & Johnson).
Commentary
GALAXI-2 and GALAXI-3 brought guselkumab, already used for ulcerative colitis, to Crohn’s disease. GRAVITI then showed that induction can be given entirely by subcutaneous injection.
Comparisons with ustekinumab within these placebo-controlled trials support the same conclusion as SEQUENCE: IL-23 p19 inhibitors appear more effective than ustekinumab.
Journal club
Design
Two identically designed phase 3, randomised (2:2:2:1), double-blind, triple-dummy, treat-through trials with placebo and active (ustekinumab) comparators (257 sites, 40 countries). 1,048 patients.
Primary result. Response plus remission, GALAXI-2: 55% (200 mg) and 49% (100 mg) vs 12% placebo; adjusted differences 43% (95% CI 32–54) and 38% (27–49); P<0.0001. GALAXI-3: 48% and 47% vs 13%; 35% (24–46) and 34% (23–45); P<0.0001.
Validity and applicability
- Head-to-head comparisons with ustekinumab were secondary endpoints.
- The primary analysis population was restricted to patients meeting SES-CD eligibility criteria added in a protocol amendment.
- Industry funded (Johnson & Johnson).
Where it sits now
IV guselkumab induction followed by SC maintenance is effective in Crohn's disease and outperformed ustekinumab at week 48 on several endpoints.
- GRAVITI (2025): Guselkumab can be given entirely by subcutaneous injection for both induction and maintenance in Crohn's disease, with no IV infusion needed.
- 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.
Questions for discussion
- The co-primary endpoints combine week-12 response with week-48 outcomes. What does a composite capture that a single time point misses, and what does it penalise?
- Superiority over ustekinumab was a secondary endpoint. How much weight would you give it, alongside SEQUENCE?
- The primary analysis was limited to patients meeting SES-CD criteria added by protocol amendment. How might that affect who these results apply to?