TREMFYA – Use of TREMFYA in Patients with Stricturing Crohn’s Disease or Stenoses

SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• In the pivotal clinical trials for patients with moderately to severely active Crohn’s disease (CD) (GALAXI 2 & 3, GRAVITI), patients with complications of CD, including symptomatic strictures or stenoses were excluded.^1,2
• A post-hoc analysis was conducted from GALAXI and GRAVITI clinical trial programs to assess treatment effect differences between TREMFYA and ustekinumab based on endoscopic clustering.^3,4
• Additionally, a case report is summarized below describing the use of TREMFYA in a patient with severe, stenotic CD.⁵

CLINICAL DATA

GALAXI/GRAVITI Phase 3 Clinical Trials

• The efficacy and safety of TREMFYA in adults with moderately to severely active CD were evaluated in the following pivotal clinical trials:^1,2
  • GALAXI 2 and 3: 2 identically designed, randomized, double-blind, active comparator, placebo-controlled treat through trials.¹
  • GRAVITI: a randomized, double-blind, placebo-controlled, parallel-group, multicenter, treat-through trial.²
• In the GALAXI and GRAVITI clinical trials, patients with complications of CD, including symptomatic strictures or stenoses were excluded.^1,2

Post-Hoc Analysis of the GALAXI/GRAVITI Clinical Trial Programs

Reinisch et al (2026)³ conducted a post hoc analysis using data from the GALAXI 2 & 3 and GRAVITI trials to assess the effect of TREMFYA in patients with nonpassable intestinal stenosis through week 96.

Study Design/Methods

• Patients included in this analysis received TREMFYA induction dose of 200 mg intravenous (IV; GALAXI 2 & 3) or 400 mg subcutaneous (SC; GRAVITI) at weeks 0, 4, and 8 followed by TREMFYA maintenance dose of 100 mg SC once every 8 weeks (Q8W) or 200 mg SC once every 4 weeks (Q4W).
• In GALAXI 2 & 3, patients were also randomized to ustekinumab. During the long-term extension (starting at week 48), patients continued their assigned maintenance dose.
• At baseline and weeks 48 & 96, centrally read endoscopies were conducted.
• At weeks 0 and 48, transcriptomic profiling of ileum biopsies in a subset of patients was performed to evaluate changes in fibroblast-associated biology.

Results

• Overall, 28.6% (315/1103) of patients across the pooled GALAXI 2 & 3 and GRAVITI studies had nonpassable intestinal stenosis at baseline. For baseline characteristics, see Table: Baseline Characteristics of Patients with Nonpassable Intestinal Stenosis.

• At week 48, an improvement to passable or no stenoses was observed among patients with nonpassable stenoses at baseline, and this improvement increased at week 96, see Table: Outcomes through Week 96 in Patients with Nonpassable Stenoses.
• In ileum samples, reductions in fibrosis-associated and inflammatory fibroblast biology were associated with improvements in ileal stenosis at week 48.
• At week 48, TREMFYA treatment significantly reduced the inflammatory and fibrosis-associated gene modules and increased epithelial- and tissue-supporting fibroblast biology; no significant changes in fibroblast biology within the ileum were observed with ustekinumab.

Richards et al (2025)⁴ conducted a post-hoc analysis using data from the GALAXI and GRAVITI trials to assess treatment effect differences between TREMFYA and ustekinumab among patients based on endoscopic clustering.

Study Design/Methods

• Endoscopic clustering was established using baseline segment SES-CD values from terminal ileum, right colon, transverse colon, left/sigmoid colon, and rectum from cohort 1 (1233 patients, GALAXI 1, GALAXI 2, GRAVITI trials) and cohort 2 (525 patients, GALAXI 3).
• Patients clusters were identified using consensus hierarchal clustering, and a machine learning classification model was developed for patient cluster assignment of cohort 2.
• GALAXI 2 and GALAXI 3 data were pooled to evaluate endoscopic outcomes at weeks 12 and 48.

Results

• Seven distinct CD endoscopic subtypes were identified: ileum only, ileum dominant, right colon dominant, mid-colon, colonic, ileocolonic, and rectum dominant.
• The identified CD endoscopic subtypes were used to stratify endoscopic remission rates along with additional clinical features, such a baseline stricturing data (SES-CD narrowing >0), to identify consolidated group with differential treatment effects.
  • Group 1 (62% of patients) had a mix of ileocolonic or colonic disease and demonstrated similar endoscopic remission rates at week 12 between TREMFYA (26%) and ustekinumab (27%), with higher remission rates for TREMFYA (39-44%) at week 48 vs ustekinumab (30%).
  • Group 2 (ileum only) and Group 3 (those with strictured right colon), accounted for 38% of patients. At week 12, higher endoscopic remission rates were reported with TREMFYA vs ustekinumab: 19% (group 2) and 20% (group 3) vs 7% (group 2) and 2% (group 3), respectively.
  • Similarly, endoscopic remission rates at week 48 were higher for TREMFYA vs ustekinumab among patients in groups 2 and 3: TREMFYA (20-26% for group 2 and 28-30% for group 3) vs ustekinumab (18% for group 2 and 12% for group 3).
  • Among patients in group 2 and 3 with baseline stricturing, endoscopic responders to TREMFYA demonstrated greater reduction in narrowing compared with non-responders at week 12, contributing to greater reduction in total SES-CD (21% vs 5%).

Case Report

Grossberg et al (2019)⁵ reported a case of a 66-year-old female with ileocolonic CD and psoriasis (PsO).

• The patient presented post ileocolonic resection with diarrhea and was previously treated with infliximab and mesalamine for both PsO and CD. Prior colonoscopy showed small ulcers at the surgical anastomosis but otherwise normal colon and neo-terminal ileum. Her dermatologist switched her treatment, as infliximab was not helping her PsO.
• After several months of ixekizumab therapy, the patient developed diarrhea and colonoscopy confirmed evidence of ulcerated, severe stenosis in the proximal descending colon that could not be traversed, along with diffuse patchy erythema in the sigmoid or descending colon.
• Biopsies revealed chronic active colitis without dysplasia in the descending colon or stricture sigmoid colon.
• Therapy was switched to ustekinumab using PsO dosing; however, follow up evaluation at 6 months demonstrated persistent narrowing and ulceration at the ileocolonic anastomosis as well as ulceration in the neo-terminal ileum despite being asymptomatic for CD symptoms and a normal colon mucosa.
• Due to suboptimal PsO control with ustekinumab, treatment was switched to TREMFYA in combination with methotrexate 15 mg weekly.
• Several months later, a follow-up colonoscopy showed deep remission, with normal colon, anastomosis, and neo-terminal ileum and normal biopsies.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 11 September 2026.