TREMFYA - Treatment of Ulcerative Colitis with Subcutaneous Induction (ASTRO Study)

SUMMARY  

• A phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled, parallel-group, treat-through study (ASTRO) evaluated the efficacy and safety of TREMFYA subcutaneous (SC) induction in adult patients with moderately to severely active ulcerative colitis (UC).^1-5
• An exploratory analysis was conducted to evaluate the clinical and endoscopic outcomes at week 48 in patients who achieved and who did not achieve clinical response to TREMFYA SC induction therapy at week 12.⁶ Pooled data from the ASTRO study were used to validate the UC bowel symptoms composite score.⁷

CLINICAL DATA

Phase 3 SC Induction Study in UC - ASTRO

Study Design/Methods

• Adults with moderately to severely active UC and a history of inadequate response (IR) or intolerance to corticosteroids, immunosuppressants (azathioprine, 6-mercaptopurine), biologics, Janus kinase inhibitors, and/or sphingosine 1-phosphate inhibitors (BIO/JAKi/S1Pi-IR) or BIO/JAKi/S1Pi-naïve were included in the study.¹
• Patients had a modified Mayo score of 5-9, a rectal bleeding subscore (RBS) ≥1, and a Mayo endoscopic subscore (MES) ≥2.^2,3
• A total of 418 patients were randomized 1:1:1 to receive:
  • TREMFYA 400 mg SC every 4 weeks (q4w) ×3→TREMFYA 200 mg SC q4w (n=140)
  • TREMFYA 400 mg SC q4w (×3)→TREMFYA 100 mg SC every 8 weeks (q8w; n=139)
  • PBO (n=139)
• Patients who met rescue criteria at week 16 were switched to the following: PBO patients were switched to TREMFYA, while TREMFYA patients remained on their assigned dose regimen (sham rescue).^2,3
• The primary endpoint was clinical remission at week 12, defined as a Mayo stool frequency subscore (SFS) of 0 or 1 (not increased from baseline), an RBS of 0, and an MES of 0 or 1 without friability.
• Multiplicity-controlled secondary endpoints at week 12 and week 24 included clinical response, symptomatic remission, and endoscopic improvement. Other multiplicity controlled secondary endpoints included histo-endoscopic mucosal improvement (HEMI) at week 12 and clinical remission (week 24).

Results through Weeks 12 and 24

• Baseline characteristics were similar across treatment groups; overall mean age, 41.7 years; mean UC duration, 7.6 years; mean modified Mayo score, 6.7; MES, 3 (56.0%); and BIO/JAKi/S1Pi-IR, 40.2%.
• At week 12, primary and secondary endpoints were achieved by a significantly higher proportion of patients treated with TREMFYA 400 mg SC induction vs PBO. For details on primary and secondary endpoints, see Table: Primary and Secondary Endpoints at Week 12 and Week 24.

• In prespecified analyses of subpopulations defined by prior history of BIO/JAKi/S1Pi, greater proportion of patients treated with TREMFYA vs PBO achieved the endpoints at weeks 12 and 24. See Table: Primary Endpoint and Secondary Endpoints at Weeks 12 and 24 in BIO/JAKi/S1Pi-Naïve and BIO/JAKi/S1Pi-IR Subgroups.

Bowel Urgency and Abdominal Pain

• An analysis was conducted to assess the severity of bowel-related symptoms using the validated Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms (UC-PRO/SS) instrument.²
• Clinically meaningful improvements (CMI) were evaluated in bowel signs and symptoms and abdominal symptoms scales.²
• Complete resolution of individual core symptoms (bowel urgency [BU] and abdominal pain [AP]) was also assessed.²

Results

• Baseline mean UC-PRO/SS domain scores were similar among treatment groups.²
• At baseline, the proportions of patients experiencing BU were²:
  • TREMFYA 100 mg q8w: 81.3%
  • TREMFYA 200 mg q4w: 84.3%
  • TREMFYA combined: 82.8%
  • PBO: 87.1%
• At baseline, the proportions of patients experiencing AP were²:
  • TREMFYA 100 mg q8w: 78.4%
  • TREMFYA 200 mg q4w: 74.3%
  • TREMFYA combined: 76.3%
  • PBO: 78.4%
• Rates of BU resolution (no BU) were²:
  • At week 12, TREMFYA combined vs PBO: 45.0% vs 23.1% (nominal P-value)
  • At week 24, TREMFYA 100 mg and 200 mg vs PBO: 47.8% and 41.5% vs 22.3% (nominal P-value)
• Rates of AP resolution (no AP) were²:
  • At week 12, TREMFYA combined vs PBO: 48.8% vs 23.9% (nominal P-value)
  • At week 24, TREMFYA 100 mg and 200 mg vs PBO: 45.9% and 45.2% vs 25.7% (nominal P-value)
• Greater proportions of patients treated with TREMFYA vs PBO had no BU, no AP, and CMI,² see Table: Change from Baseline and CMI from Baseline in Bowel-Related Symptoms.

• For safety through week 24, see Table: Safety through Week 24.

Results through Week 48

• For efficacy results through week 48 in the overall population and in subpopulations defined by prior history of BIO/JAKi/S1Pi, see Table: Efficacy at Week 48.³

• Safety events per 100 patient-years were lower in TREMFYA groups vs placebo. See Table: Safety at Week 48.³

Additional Analyses

Exploratory Analyses of Clinical and Endoscopic Endpoints at Week 48 According to Clinical Response Status at Week 12

Study Design/Methods

• Exploratory analyses were conducted to evaluate clinical and endoscopic endpoints at week 48 among patients with and without clinical response to TREMFYA induction therapy at week 12.⁶
  • Clinical response was defined as a decrease from baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the RBS or achieving a RBS of 0 or 1. Responders were defined as patients who were in clinical response at week 12 and received treatment from week 12. Nonresponders were defined as patients who were not in clinical response and clinical remission at week 12 and received treatment from week 12.
  • Clinical remission was defined as a Mayo SFS of 0 or 1 and that had not increased from baseline, a Mayo RBS of 0, and an MES of 0 or 1 with no friability.
  • Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability.
  • Endoscopic remission was defined as an endoscopy subscore of 0.

Results

• Among the 267 patients treated with TREMFYA, 67.4% attained clinical response to TREMFYA induction therapy at week 12.⁶
• For efficacy outcomes through week 48 defined by week 12 responders and nonresponders, see Table: Efficacy at Week 48 by TREMFYA Clinical Response at Week 12.

Patient Reported Outcomes (PROs) of Bowel Symptoms

Study Design/Methods

• Validation of a new PRO composite endpoint was evaluated which includes stool frequency (SF), rectal bleeding (RB), BU, and AP using daily diary data from the UC-PRO/SS instrument.⁷
• To calculate the UC bowel symptoms composite score, pooled data from the TREMFYA and PBO groups collected from week 0 to week 12 were used.
• Patients answered the UC/PRO-SS electronic questionnaire daily for 10 consecutive days before q4w clinical study visits from week 0 to week 12.
• A UC-PRO/SS score of 0 indicated no symptoms and that of 19 indicated worst severity (SF (range: 0-7), RB (0-4), BU (0-4), and AP (0-4)).
• Complete bowel symptomatic remission (CBSR) was defined as RBS=0, BU=0, AP=0, and SF ≤4 times daily.
• For the validation analysis, the IBDQ and 29-item PROMIS-29 were used as anchors. Rates of week 12 endoscopic endpoints were reported in subgroups with and without CBSR.

Results

• For the proportions of patients who experienced bowel symptoms at baseline and week 12, see Table: Bowel Symptoms at Baseline and Week 12.
• Endoscopic outcomes based on the CBSR status are summarized in Table: Endoscopic Outcomes and HRQoL Based on the CBSR Status.

Pharmacokinetics

Peyrin-Biroulet et al (2025)⁴ evaluated the impact of SC TREMFYA induction on molecular inflammation from baseline (week 0) to week 12 in patients with UC.

Study Design/Methods

• The intravenous (IV) induction dosing regimen for phase 2b/3 QUASAR studies included 200 mg q4w ×3 and SC induction for ASTRO study included 400 mg q4w ×3.
• Both QUASAR and ASTRO studies used the same SC maintenance dosing regimens (100 mg q8w or 200 mg q4w).
• To compare TREMFYA pharmacokinetic (PK) exposure following 200 mg IV vs 400 mg SC induction through week 12, individual post hoc PK parameters and patient dosing information from QUASAR and ASTRO were used to simulate concentration-time profile and calculate individual induction exposure metrics.
  • PK parameters were estimated with the established QUASAR 2-compartment linear population PK (popPK) model with first-order absorption and elimination.
• For key week 12 efficacy endpoints (clinical remission, clinical response, endoscopic improvement, and HEMI), comparative graphical exposure-response(E-R) analysis (QUASAR vs ASTRO) was conducted using average concentration from week 0 to week 12 (induction) (C_{ave, week 0-12}) and associated exposure quartiles from the combined study populations.
• Clinical response was defined as a ≥30% reduction and a ≥2-point decrease from induction baseline in the modified Mayo score, with either a ≥1-point decrease in the RBS or an RBS of 0 or 1.
• Clinical remission was defined as an SFS of 0 or 1 (with no increase from induction baseline), an RBof 0, and an endoscopy subscore of 0 or 1 without friability.
• Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 without friability.
• HEMI was defined as a combination of histologic and endoscopic healing, where histologic healing was defined as neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue per the Geboes grading system.

Results

• SC induction resulted in similar average serum concentrations and area under the concentration-time curve (AUC) from week 0 to week 12, lower peak concentrations at week 8, and higher trough levels at week 12 compared with IV induction. These are consistent with model predictions. For details, see Table: Comparison of Model-Predicted TREMFYA PK Exposures at Week 12 After IV and SC Induction Regimens.

• Steady-state serum concentration of TREMFYA was achieved by week 24.
• Simulations based on the popPK model showed that serum TREMFYA levels were comparable by week 24 regardless of the induction route, when followed by the same maintenance regimen.
• At week 12, efficacy outcomes were comparable across TREMFYA concentration quartiles for both IV and SC induction. For details, see Figures: Clinical Response at Week 12 by GUS C_{ave, week 0-12} Quartile (μg/mL), Clinical Remission at Week 12 by GUS C_{ave, week 0-12} Quartile (μg/mL), Endoscopic Improvement at Week 12 by GUS C_{ave, week 0-12} Quartile (μg/mL), and Histologic Endoscopic Mucosal Improvement at Week 12 by GUS C_{ave, week 0-12} Quartile (μg/mL).

Molecular Analyses

Venkat et al (2025) evaluated the impact of SC TREMFYA induction on molecular inflammation from baseline (week 0) to week 12 in patients with UC.⁵

• Analyses were conducted to assess molecular changes from baseline to week 12 among patients in the ASTRO randomized population. Specifically, transcriptional profiling of colonic biopsies from 339 patients was performed.
• A comparative analysis with biopsy samples from 593 patients from the QUASAR induction study was also performed.
• Correlation between Geboes score and changes in transcriptional gene modules were evaluated in colonic biopsies from 413 patients.
• Molecular changes were assessed in the context of clinical remission and HEMI at week 12.

Results

• At week 12, treatment with TREMFYA SC induction (ASTRO) resulted in significant downregulation of inflammatory transcriptional modules in colon tissue, representing T- helper 17 [Th17], interferon-gamma [IFN-γ] signaling, inflamed epithelium, plasma cell, neutrophil and inflammatory fibroblast biology, and upregulation of healthy epithelium-related gene modules including goblet cells and healthy epithelium (all false discovery rate [FDR]<0.05).
• Response to TREMFYA SC induction showed significant correlation with changes observed with transcriptional genes modules with TREMFYA 200 mg IV induction in QUASAR (R=0.98, P<0.0001).
• Patients achieving clinical remission or HEMI at week 12 showed robust changes in gene module expression, nearing non-inflammatory bowel disease (non-IBD) control levels (P<0.0001) compared to nonremitters. This molecular response was consistent across subgroups defined by prior exposure to BIO/JAKi/S1Pi, in both treatment-naïve and treatment-resistant patients (R=0.93, P<0.0001).
• At week 12, serum and tissue interleukin-22 (IL-22) levels were significantly decreased (P<0.05) in 355 patients, nearing non-IBD control levels both with TREMFYA SC induction and IV induction.
• Patients who achieved clinical remission at week 12 showed a robust reduction in Geboes histologic scores (P<0.05) compared to nonremitters.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 21 January 2026.