Guselkumab and Intestinal Stenosis in Crohn’s Disease, With David Rubin, MD

Patients with moderately to severely active Crohn’s disease (CD) and non-passable intestinal stenosis at baseline had improvement to passable or no stenosis with guselkumab, with gains growing from week 48 to week 96. These post hoc results from the phase 3 GALAXI 2 and 3 and GRAVITI studies were presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.¹

Translational analyses also showed guselkumab reduced inflammatory and fibrosis-associated fibroblast gene activity in the ileum, while ustekinumab showed limited changes.¹ David Rubin, MD, of the University of Chicago Medicine Inflammatory Bowel Disease Center, told HCPLive narrowing in CD is not always fibrotic, and recognizing the difference matters for treatment.

“The distinction between a stenosis that’s not fibrotic or is only partially fibrotic, and a stenosis that is too fibrotic to respond to anti-inflammatory therapy is very important,” said Rubin.

Intestinal Stenosis Burden in Crohn’s Disease

Intestinal stenosis can cause obstructive symptoms including cramping, pain, nausea, and vomiting, and often leads to dilation or surgery. Evidence on whether biologics can improve stenosis remains limited.¹

Guselkumab, a dual-acting interleukin-23p19 subunit inhibitor, received US Food and Drug Administration approval for moderately to severely active CD in March 2025. It was the first IL-23 inhibitor approved with both intravenous (IV) and subcutaneous (SC) induction options.⁴

GALAXI and GRAVITI Stenosis Analysis Design

GALAXI 2 and 3 evaluated guselkumab 200 mg IV induction, and GRAVITI evaluated 400 mg SC induction, each at weeks 0, 4, and 8.²,³ Maintenance was 100 mg SC every 8 weeks or 200 mg SC every 4 weeks, and GALAXI also included an ustekinumab arm. Patients with symptomatic stenoses or stenoses requiring surgery were excluded from enrollment.¹

Stenosis status was graded using the narrowing component of the Simple Endoscopic Score for Crohn’s Disease (SES-CD), with a score of 3 indicating a non-passable narrowing. Across the pooled studies, 315 of 1103 patients (28.6%) randomized to active treatment had non-passable stenosis at baseline.¹ Rubin noted stenosis is already captured in the SES-CD, so the analysis relied on data collected routinely in the trials.

Stenosis Improvement With Guselkumab Through Week 96

In GALAXI, 33.5% of guselkumab-treated patients with non-passable stenosis at baseline improved to passable or no stenosis by week 12.¹ By week 48, 43.9% of patients receiving guselkumab 100 mg and 41.9% receiving 200 mg had improved, rising to 47.6% and 51.5%, respectively, at week 96.

Complete resolution to no stenosis at week 96 occurred in 38.1% and 44.1% of patients in the 100 mg and 200 mg groups, respectively.¹ Patients receiving ustekinumab also improved, with 38.9% reaching passable or no stenosis at week 96.

In GRAVITI, non-passable stenosis persisted at week 96 in 40.0% of patients receiving guselkumab 100 mg and 51.7% receiving 200 mg.¹ Rubin added few patients developed new stenoses after treatment, countering a long-held concern healing might cause new narrowing.

Fibroblast Biology Changes Linked to Stenosis Improvement

RNA sequencing of ileal biopsies from a GALAXI subset showed improvement in ileal stenosis was associated with reductions in fibrosis-associated and inflammatory fibroblast gene modules.¹ Guselkumab significantly reduced inflammatory fibroblast activity by week 12, followed by further reductions in fibrosis-related biology by week 48. It also increased gene modules linked to epithelial- and mucosa-supporting fibroblasts.

Ustekinumab showed no significant changes in ileal fibroblast biology.¹ Rubin said the biomarker work is preliminary but may eventually help identify which patients with stenosis are likely to respond to medical therapy.

“We don’t want to just give people who are obstructed or partially obstructed medical therapy and hope it’s going to work,” said Rubin.

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

References

1. Reinisch W, Afzali A, Bassiri H, et al. Changes in intestinal stenosis among patients with moderately to severely active Crohn’s disease treated with guselkumab: results from the phase 3 GALAXI and GRAVITI studies. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. Panaccione R, Feagan BG, Afzali A, et al. Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn’s disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials. Lancet. 2025;406(10501):358-375. doi:10.1016/S0140-6736(25)00681-6

3. Hart A, Panaccione R, Steinwurz F, et al. 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. Gastroenterology. 2025;169(2):308-325. doi:10.1053/j.gastro.2025.02.033

4. U.S. FDA approves Tremfya (guselkumab), the first and only IL-23 inhibitor offering both subcutaneous and intravenous induction options for adult patients with moderately to severely active Crohn’s disease. News release. Johnson & Johnson. March 20, 2025. Accessed October 19, 2026. https://www.jnj.com/media-center/press-releases/u-s-fda-approves-tremfya-guselkumab-the-first-and-only-il-23-inhibitor-offering-both-subcutaneous-and-intravenous-induction-options-for-adult-patients-with-moderately-to-severely-active-crohns-disease