QUASARUC · Induction and maintenance
Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies
Rubin DT, et al.
Lancet 2025 · PMID 39706209 (PubMed, opens in a new tab) · doi 10.1016/S0140-6736(24)01927-5 (full paper, opens in a new tab)
| Endpoint | Guselkumab IV | 200 mg SC every 4 weeks | 100 mg SC every 8 weeks | Placebo | Difference |
|---|---|---|---|---|---|
| Clinical remission, Induction · week 12 (primary endpoint) | 23% (95/421) | not in this comparison | not in this comparison | 8% (22/280) | Adjusted difference 15% (95% CI 10–20); P<0.0001 |
| Clinical remission, Maintenance · week 44 (primary endpoint) | not in this comparison | 50% (95/190) | 45% (85/188) | 19% (36/190) | Adjusted differences 30% (95% CI 21–38) and 25% (16–34) vs placebo; both P<0.0001 |
Source: Rubin 2025, abstract. In maintenance, placebo means withdrawal of guselkumab after response to induction. Differences are adjusted.
Structured abstract
BackgroundIL-23 inhibition was known to work in UC. Guselkumab, an IL-23 p19 antibody that can also bind CD64, needed phase 3 testing as induction and maintenance therapy.
MethodsPhase 3, randomised, double-blind, placebo-controlled: 12-week IV induction (3:2) and 44-week SC randomised-withdrawal maintenance (1:1:1). 701 patients. Primary endpoint: Clinical remission at induction week 12 and maintenance week 44.
ResultsPrimary result. Induction: 23% (95/421) vs 8% (22/280); adjusted difference 15% (95% CI 10–20); P<0.0001. Maintenance: 50% (200 mg every 4 weeks) and 45% (100 mg every 8 weeks) vs 19%; differences 30% (95% CI 21–38) and 25% (95% CI 16–34); both P<0.0001.
Take-homeGuselkumab induces and maintains remission in UC, and the follow-up ASTRO trial showed induction can be given subcutaneously.
| Patients | 701 |
|---|---|
| Population | Adults with moderately to severely active UC (modified Mayo 5–9) and inadequate response or intolerance to conventional or advanced therapy. Maintenance: 568 week-12 responders to IV guselkumab (from the phase 2b and phase 3 induction studies). |
| Comparison | Guselkumab 200 mg IV at weeks 0, 4 and 8 vs placebo; responders randomised to 200 mg SC every 4 weeks, 100 mg SC every 8 weeks, or placebo (withdrawal) |
| Drugs | guselkumab |
| Classes | Anti-IL-23 (p19) |
| Published | Rubin DT, et al. Lancet 2025;405:33–49. |
Key points
- Induction serious adverse events: 3% with guselkumab vs 7% with placebo; adverse events 49% in both groups.
- No active tuberculosis, anaphylaxis, serum sickness or clinically important liver disorders in either study.
- Guselkumab is an IgG1 IL-23 p19 antibody that can also bind CD64, which the authors call dual-acting.
Limitations
- Maintenance used randomised withdrawal of induction responders.
- No active comparator.
- Whether CD64 binding gives any clinical advantage over other p19 antibodies is unproven.
Commentary
What came after. ASTRO (PMID 41544637) tested subcutaneous guselkumab induction (400 mg at weeks 0, 4 and 8) and found 28% vs 6% clinical remission at week 12, allowing a fully subcutaneous regimen. VEGA (PMID 36738762) tested guselkumab combined with golimumab for induction.
Related. Mirikizumab (LUCENT, PMID 37379135) and risankizumab (INSPIRE and COMMAND, PMID 39037800).
Journal club
Design
Phase 3, randomised, double-blind, placebo-controlled: 12-week IV induction (3:2) and 44-week SC randomised-withdrawal maintenance (1:1:1). 701 patients.
Primary result. Induction: 23% (95/421) vs 8% (22/280); adjusted difference 15% (95% CI 10–20); P<0.0001. Maintenance: 50% (200 mg every 4 weeks) and 45% (100 mg every 8 weeks) vs 19%; differences 30% (95% CI 21–38) and 25% (95% CI 16–34); both P<0.0001.
Validity and applicability
- Maintenance used randomised withdrawal of induction responders.
- No active comparator.
- Whether CD64 binding gives any clinical advantage over other p19 antibodies is unproven.
Where it sits now
Guselkumab induces and maintains remission in UC, and the follow-up ASTRO trial showed induction can be given subcutaneously.
- 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.
- 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.
- ARTEMIS-UC (2024): Anti-TL1A therapy is a new mechanism in UC; tulisokibart produced a large placebo-adjusted remission rate in a short phase 2 trial, with phase 3 results still awaited.
Questions for discussion
- Maintenance randomised responders from both the phase 2b and phase 3 induction studies. How does that affect whom the maintenance results apply to?
- The two maintenance doses gave similar remission rates. How would you choose between them?
- Without a head-to-head trial, how would you choose among the IL-23 p19 antibodies for UC?