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Subcutaneous Guselkumab Induction Achieves Clinical Remission in 28% of Ulcerative Colitis Patients vs 6% Placebo
In a phase 3 placebo-controlled trial, subcutaneous guselkumab induction therapy produced clinical remission at week 12 in 28% of participants with moderately to severely active ulcerative colitis compared with just 6% receiving placebo — an adjusted treatment difference of 21 percentage points (95% CI 14–28; p<0.0001). Remission rates were sustained through week 24 in both dosing regimens, with a safety profile broadly comparable to placebo, supporting a fully subcutaneous approach as a viable induction and maintenance strategy.
What Was Studied
The ASTRO trial investigated whether guselkumab — an IL-23p19 subunit inhibitor currently requiring intravenous dosing for induction in ulcerative colitis — could achieve clinical remission when administered entirely via the subcutaneous route. The primary outcome was clinical remission at week 12, defined as a Mayo stool frequency subscore of 0 or 1 (not increased from baseline), a rectal bleeding subscore of 0, and an endoscopic subscore of 0 or 1 without friability, evaluated across two subcutaneous guselkumab dosing regimens compared with placebo.
How It Was Studied
ASTRO was a double-blind, treat-through, randomised, placebo-controlled phase 3 trial conducted across 153 sites in 25 countries, enrolling 418 adults aged 18 years or older with moderately to severely active ulcerative colitis (modified Mayo score 5–9, Mayo endoscopic subscore ≥2, rectal bleeding subscore ≥1) who had a current or prior history of inadequate response or intolerance to corticosteroids, azathioprine, 6-mercaptopurine, biologics, JAK inhibitors, or sphingosine 1-phosphate receptor inhibitors, or corticosteroid dependence. Participants were randomised 1:1:1 to subcutaneous guselkumab 400 mg at weeks 0, 4, and 8 followed by either 100 mg every 8 weeks (400/100 mg group, n=139) or 200 mg every 4 weeks (400/200 mg group, n=140), or matched subcutaneous placebo (n=139). Stratification was by prior biologic, JAK inhibitor, or S1P inhibitor failure and baseline endoscopic severity. A treat-through design was employed, with participants meeting rescue criteria at week 16 transitioning to active guselkumab or continuing their assigned regimen via sham rescue; safety was followed through week 24.
What Was Observed
- Primary endpoint — clinical remission at week 12: Pooled across both guselkumab arms, 28% of participants (77 of 279) achieved clinical remission compared with 6% on placebo (9 of 139), representing an adjusted treatment difference of approximately 21 percentage points (95% CI 14–28; p<0.0001) — a highly statistically significant and clinically meaningful separation.
- Sustained remission at week 24: Clinical remission was maintained through week 24 in 35% of the 400/100 mg group and 36% of the 400/200 mg group, versus 9% in the placebo group, with both guselkumab groups showing statistically significant superiority over placebo at this timepoint.
- Overall and serious adverse events: Overall adverse event rates were similar across groups — 53% in the 400/100 mg arm, 61% in the 400/200 mg arm, and 65% in the placebo group. Serious adverse events were notably less frequent in the guselkumab arms (4% each) than in the placebo arm (12%), driven in part by higher rates of ulcerative colitis worsening in the placebo group (21%) versus the guselkumab arms (10% and 6%, respectively).
- No new safety signals: There were no treatment-related deaths and no previously unrecognised safety concerns. The most common adverse events — arthralgia and upper respiratory tract infection — occurred at low and broadly comparable frequencies across all groups.
Why This Matters
All currently approved IL-23p19 inhibitors for ulcerative colitis, including guselkumab itself in other indications, require intravenous administration for induction — a logistical and access burden for patients and healthcare systems alike. Demonstrating that a fully subcutaneous induction and maintenance regimen can achieve meaningful and sustained remission rates potentially eliminates the need for infusion-centre visits during the induction phase. This finding expands the options available within the biologic treatment landscape for inflammatory bowel disease and may particularly benefit patients in settings where intravenous administration is less accessible.
How to Read This Result
This is a well-designed, high-quality phase 3 randomised controlled trial with clear efficacy signals and a reassuring short-term safety profile; however, the trial remains ongoing and data beyond 24 weeks — including longer-term durability and comparative maintenance regimen performance — are not yet available, and the treat-through design may limit direct interpretation of the maintenance phase comparisons.
Limitations
The abstract does not explicitly report study limitations.