GRAVITICD · Induction and maintenance
Efficacy and Safety of Guselkumab Subcutaneous Induction and Maintenance in Participants With Moderately to Severely Active Crohn's Disease: Results From the Phase 3 GRAVITI Study
Hart A, et al.
Gastroenterology 2025 · PMID 40113101 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2025.02.033 (full paper, opens in a new tab)
| Endpoint | Guselkumab | 100 mg every 8 weeks | 200 mg every 4 weeks | Placebo | Difference |
|---|---|---|---|---|---|
| Clinical remission, Week 12 · both guselkumab groups pooled (primary endpoint) | 56.1% | not in this comparison | not in this comparison | 21.4% | Difference 34.9 points; P<0.001 |
| Endoscopic response, Week 12 · both guselkumab groups pooled (primary endpoint) | 41.3% | not in this comparison | not in this comparison | 21.4% | Difference 19.9 points; P<0.001 |
| Clinical remission, Week 48 · by maintenance dose | not in this comparison | 60.0% | 66.1% | 17.1% | Differences 42.8 and 48.9 points; P<0.001 each |
| Endoscopic response, Week 48 · by maintenance dose | not in this comparison | 44.3% | 51.3% | 6.8% | Differences 37.5 and 44.6 points; P<0.001 each |
Source: Hart 2025, abstract. Differences vs placebo as printed, without CIs. Placebo patients meeting rescue criteria received guselkumab from week 16.
Structured abstract
BackgroundGuselkumab had been studied in Crohn's disease with IV induction; GRAVITI tested whether induction could be given entirely by subcutaneous injection.
MethodsPhase 3, randomised (1:1:1), double-blind, placebo-controlled, treat-through trial. 347 patients. Primary endpoint: Co-primary at week 12: clinical remission and endoscopic response.
ResultsPrimary result. Clinical remission 56.1% vs 21.4% (difference 34.9; P<0.001); endoscopic response 41.3% vs 21.4% (difference 19.9; P<0.001).
Take-homeGuselkumab can be given entirely by subcutaneous injection for both induction and maintenance in Crohn's disease, with no IV infusion needed.
| Patients | 347 |
|---|---|
| Population | Adults with moderately to severely active Crohn's disease, both biologic-naive and with inadequate response or intolerance to biologics. |
| Comparison | Subcutaneous guselkumab induction and maintenance vs placebo |
| Drugs | guselkumab |
| Classes | Anti-IL-23 p19 |
| Published | Hart A, et al. Gastroenterology 2025;169:308–25. |
Key points
- Guselkumab 400 mg SC every 4 weeks for induction, then 100 mg SC every 8 weeks (n=115) or 200 mg SC every 4 weeks (n=115); placebo n=117.
- Week 48 clinical remission: 60.0% (100 mg every 8 weeks; difference 42.8) and 66.1% (200 mg every 4 weeks; difference 48.9) vs 17.1% placebo (P<0.001 each).
- Week 48 endoscopic response: 44.3% (difference 37.5) and 51.3% (difference 44.6) vs 6.8% placebo (P<0.001 each).
- All multiplicity-controlled endpoints were met; efficacy was seen in biologic-naive and biologic-experienced patients.
- Adverse event rates were not greater with guselkumab than with placebo. Placebo patients meeting rescue criteria received guselkumab from week 16.
Limitations
- Placebo-controlled; no active comparator.
- Relatively small trial for a phase 3 program; the IV-induction data are in GALAXI-2 and GALAXI-3.
- Industry funded (Johnson & Johnson).
Commentary
GRAVITI is practice-relevant because it removes the need for an infusion clinic visit to start therapy. Compare it with the IV-induction program in GALAXI-2 and GALAXI-3.
Journal club
Design
Phase 3, randomised (1:1:1), double-blind, placebo-controlled, treat-through trial. 347 patients.
Primary result. Clinical remission 56.1% vs 21.4% (difference 34.9; P<0.001); endoscopic response 41.3% vs 21.4% (difference 19.9; P<0.001).
Validity and applicability
- Placebo-controlled; no active comparator.
- Relatively small trial for a phase 3 program; the IV-induction data are in GALAXI-2 and GALAXI-3.
- Industry funded (Johnson & Johnson).
Where it sits now
Guselkumab can be given entirely by subcutaneous injection for both induction and maintenance in Crohn's disease, with no IV infusion needed.
- 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.
- 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.
- VIVID-1 (2024): Mirikizumab, an IL-23 p19 inhibitor, induces and maintains clinical and endoscopic response in Crohn's disease, including after biologic failure.
Questions for discussion
- Placebo rates at week 12 were 21.4% for both clinical remission and endoscopic response. What drives placebo response in Crohn's trials, and how does it differ between symptom and endoscopic endpoints?
- Placebo patients meeting rescue criteria switched to guselkumab at week 16. How would you expect them to be counted at week 48, and how does that affect the week-48 differences?
- With both SC and IV induction available, which patients would you still bring in for infusions?