Guselkumab Sustains Histologic Healing in Ulcerative Colitis Over 3 Years

Most patients with moderately to severely active ulcerative colitis (UC) who reached histologic remission on guselkumab maintained it through 3 years, according to a post hoc analysis of the QUASAR long-term extension (LTE). The findings were presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.1

Among patients in histologic remission at the start of maintenance, 75.9% receiving guselkumab 100 mg every 8 weeks and 81.3% receiving 200 mg every 4 weeks remained in histologic remission at maintenance week 140.1

Although histologic outcomes are frequently reported in UC trials, long-term changes over multiple years have not been well characterized.1 David Rubin, MD, of the University of Chicago Medicine Inflammatory Bowel Disease Center, told HCPLive the analysis shows histologic remission is achievable in most responders and relatively stable once reached.

QUASAR Long-Term Extension Design and Histologic Assessment

QUASAR enrolled adults with a modified Mayo score of 5 to 9, a rectal bleeding subscore ≥ 1, and an endoscopic subscore of 2 or 3.1 Patients in clinical response 12 weeks after intravenous guselkumab induction were randomly assigned in a 1:1:1 ratio to subcutaneous guselkumab 100 mg every 8 weeks, 200 mg every 4 weeks, or placebo. In the primary maintenance analysis, clinical remission at week 44 was achieved by 45% and 50% of patients receiving guselkumab, respectively, vs 19% with placebo.2

Patients receiving 100 mg who lost response between maintenance weeks 8 and 32 received a blinded dose adjustment to 200 mg every 4 weeks. Biopsies were collected at induction baseline and at maintenance weeks 0, 44, 92, and 140, and scored using the Geboes system. The analysis included 137 patients in the 100-mg group and 130 in the 200-mg group with evaluations at every time point.1

Histologic remission was defined as the absence of neutrophils in the lamina propria and epithelium, with no crypt destruction, erosions, ulcerations, or granulation tissue. In the LTE randomized population, 38.7% and 41.9% of patients had a prior inadequate response or intolerance to advanced therapy.1

Histologic Improvement Through 3 Years of Guselkumab

At induction baseline, 91.9% of patients in the 100-mg group and 86.1% in the 200-mg group had Geboes scores of 3.2 to 5.4. After 12 weeks of intravenous induction, 62.7% and 63.9%, respectively, had Geboes scores of 0.0 to 3.1. This proportion rose to 76.6% and 83.9% at maintenance week 44 and held at 79.6% and 83.1% at week 140.1

The proportion of patients with the most severe Geboes scores of 5.3 or 5.4 fell from 28.4% and 26.1% at induction baseline to 5.8% and 6.9% at maintenance week 0, reaching 3.6% and 2.3% at week 140.1

At the start of maintenance, 56.4% (79/140) of patients receiving 100 mg and 57.3% (75/131) receiving 200 mg were in histologic remission. Of these, 75.9% (60/79) and 81.3% (61/75) remained in remission at week 140, and 53.2% (42/79) and 61.3% (46/75) were in remission at every maintenance time point.1

“If you had histological remission at the end of 1 year, you were likely to still be there at the ends of 2 and 3 years,” Rubin explained.

He noted most gains occurred within the first year of treatment, with little additional improvement afterward. He added the 200-mg dose appeared numerically more effective, although the analysis was not powered to compare doses.

Histology, Endoscopy, and Treatment Targets in UC

The investigators reported histologic improvement trends over time were similar to previously reported endoscopic trends in QUASAR.1 Rubin said Mayo endoscopic scores appeared less healed than histology at corresponding time points, and he outlined possible explanations, including histologic improvement preceding visible mucosal healing.

“My own hypothesis is that it starts with histological improvement,” said Rubin. “That’s where the therapy might be working directly and having an effect, and the mucosa catches up later, and that might be why we’re seeing what we see.”

Rubin said the next step is determining whether treatment decisions should be guided by symptoms, endoscopy, histology, or all 3. He pointed to the VERDICT trial of vedolizumab, being presented at United European Gastroenterology Week, as a complementary study testing whether targeting histologic remission improves outcomes.

Editors’ note: Rubin reports relevant disclosures with AbbVie, Abivax, Bristol Myers Squibb, Celltrion, Eli Lilly, Genentech, J&J, and others.

References:

1. Rubin DT, Allegretti JR, Alvarez Y, et al. Histology outcomes over time in patients with moderately to severely active ulcerative colitis treated with guselkumab in the QUASAR long-term extension study. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. Rubin DT, Allegretti JR, Panés J, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49. doi:10.1016/S0140-6736(24)01927-5