Landmark IBD trials · Summary of an original articleLancet Gastroenterol Hepatol 2026;11:284–98

ASTROUC · Induction and maintenance

Efficacy and safety of subcutaneous guselkumab induction therapy in participants with moderately to severely active ulcerative colitis (ASTRO): a double-blind, treat-through, randomised, placebo-controlled, phase 3 trial

Long M, et al.

Lancet Gastroenterol Hepatol 2026 · PMID 41544637 (PubMed, opens in a new tab) · doi 10.1016/S2468-1253(25)00322-X (full paper, opens in a new tab)

Figure 1. Clinical remission with fully subcutaneous guselkumab: at week 12 after 400 mg at weeks 0, 4 and 8 (both guselkumab groups pooled), and at week 24 by maintenance dose (100 mg every 8 weeks or 200 mg every 4 weeks).

Data for this figure, percentage of patients
Endpoint	Guselkumab	400/100 mg	400/200 mg	Placebo	Difference
Clinical remission, Week 12 · both guselkumab groups pooled (primary endpoint)	28% (77/279)	not in this comparison	not in this comparison	6% (9/139)	Adjusted difference +21 points (95% CI 14–28); P<0.0001
Clinical remission, Week 24 · by maintenance dose	not in this comparison	35% (49/139)	36% (51/140)	9% (13/139)	Both guselkumab groups significantly better than placebo

Source: Long 2026, abstract. Placebo patients meeting rescue criteria received guselkumab from week 16; the abstract does not give a CI for the week-24 differences.

Structured abstract

BackgroundIL-23 p19 antibodies, including guselkumab, needed IV induction in UC; a fully subcutaneous regimen would avoid infusion visits.

MethodsPhase 3, double-blind, treat-through, randomised (1:1:1), placebo-controlled trial (153 sites, 25 countries). 418 patients. Primary endpoint: Clinical remission at week 12 (stool frequency 0–1 and not above baseline, rectal bleeding 0, endoscopic subscore 0 or 1 without friability).

ResultsPrimary result. 28% (77/279) vs 6% (9/139); adjusted difference 21 percentage points (95% CI 14–28); P<0.0001

Take-homeGuselkumab can be started with subcutaneous 400 mg injections instead of IV infusions, with clear benefit over placebo by week 12.

Table 1. Trial at a glance

Patients	418
Population	Adults with moderately to severely active UC (modified Mayo 5–9, endoscopic subscore ≥2, rectal bleeding subscore ≥1) and inadequate response or intolerance to corticosteroids, thiopurines, biologics, JAK inhibitors or S1P modulators, or corticosteroid dependence
Comparison	Guselkumab 400 mg SC at weeks 0, 4 and 8, then 100 mg every 8 weeks or 200 mg every 4 weeks, vs placebo
Drugs	guselkumab
Classes	Anti-IL-23 (p19)
Published	Long M, et al. Lancet Gastroenterol Hepatol 2026;11:284–98.

Key points

Week 24 clinical remission: 35% (400/100 mg) and 36% (400/200 mg) vs 9% with placebo (both significant).
Serious adverse events: 4% and 4% with guselkumab vs 12% with placebo; worsening UC 10% and 6% vs 21%.
Adverse events overall: 53% (400/100 mg) and 61% (400/200 mg) vs 65% (placebo).
Until ASTRO, approved IL-23 p19 antibodies all required IV induction in UC (as the authors note).

Limitations

Results reported to week 24 only; the trial is ongoing.
No IV induction comparator, so SC and IV induction were not compared directly.
Placebo patients meeting rescue criteria crossed over at week 16, limiting later placebo comparisons.

Commentary

Context. IV induction requires an infusion clinic, which adds cost and delay. ASTRO showed a fully subcutaneous guselkumab regimen works. The IV-induction phase 3 programme is QUASAR (PMID 39706209), where week-12 remission was 23% vs 8%.

Canada. Check the current Canadian product monograph and coverage for subcutaneous induction before prescribing it.

Journal club

PopulationAdults with moderately to severely active UC (modified Mayo 5–9, endoscopic subscore ≥2, rectal bleeding subscore ≥1) and inadequate response or intolerance to corticosteroids, thiopurines, biologics, JAK inhibitors or S1P modulators, or corticosteroid dependence

InterventionGuselkumab 400 mg SC at weeks 0, 4 and 8, then 100 mg every 8 weeks or 200 mg every 4 weeks,

ComparisonPlacebo

Primary outcomeClinical remission at week 12 (stool frequency 0–1 and not above baseline, rectal bleeding 0, endoscopic subscore 0 or 1 without friability)

Design

Phase 3, double-blind, treat-through, randomised (1:1:1), placebo-controlled trial (153 sites, 25 countries). 418 patients.

Primary result. 28% (77/279) vs 6% (9/139); adjusted difference 21 percentage points (95% CI 14–28); P<0.0001

Validity and applicability

Results reported to week 24 only; the trial is ongoing.
No IV induction comparator, so SC and IV induction were not compared directly.
Placebo patients meeting rescue criteria crossed over at week 16, limiting later placebo comparisons.

Where it sits now

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.
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

Week-12 remission was 28% here and 23% with IV induction in QUASAR. Why can't you conclude that SC and IV induction are equivalent from two separate trials?
Placebo patients could be rescued with guselkumab at week 16. How does that affect the week-24 comparison?
When would you still choose IV induction for a patient with UC?

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