Johnson & Johnson has released compelling long-term clinical evidence demonstrating that TREMFYA (guselkumab), a dual-acting monoclonal antibody, maintains sustained clinical and endoscopic remission in patients with moderately to severely active ulcerative colitis through three years of continuous treatment. The findings, presented at the European Crohn’s and Colitis Organisation (ECCO) 2026 conference, represent a significant advancement in inflammatory bowel disease management and offer new hope for UC patients seeking long-lasting disease control.
Study Overview: QUASAR Long-Term Extension Program
The QUASAR long-term extension (LTE) study evaluated the efficacy and safety profile of TREMFYA in adults with moderate-to-severe ulcerative colitis who had previously demonstrated inadequate response or intolerance to conventional therapies. The study population included patients who had failed or were unable to tolerate conventional treatments such as thiopurines, corticosteroids, TNF antagonists, vedolizumab, and JAK inhibitors.
The three-year study period represented a comprehensive assessment of the drug’s sustained effectiveness and safety profile, with data collected through Week 140 of the clinical trial. Approximately 89% of eligible study participants successfully completed treatment through Week 140, demonstrating strong patient retention and tolerability throughout the extended study period.
Breakthrough Results: Clinical Efficacy at Week 140
Clinical Remission Rates
The results showcase impressive clinical outcomes that exceed many current treatment standards for ulcerative colitis. At Week 140 of the QUASAR long-term extension study:
- 80.8% of patients achieved clinical remission, defined as a Mayo stool frequency subscore of 0 or 1 (without increase from baseline), a Mayo rectal bleeding subscore of 0, and a Mayo endoscopic subscore of 0 or 1.
- 87.5% of patients who achieved clinical remission at Week 44 maintained clinical remission through Week 140, indicating robust sustained efficacy.
- Nearly all patients (approximately 95%+) who achieved clinical remission were corticosteroid-free for at least eight weeks, reducing dependency on systemic corticosteroid therapy.
Endoscopic and Histologic Outcomes
Beyond symptomatic improvement, TREMFYA demonstrated remarkable tissue-level healing:
- 53.6% of patients achieved complete endoscopic remission (Mayo Endoscopic Score of 0), representing normalization of the colon lining as visualized during endoscopy.
- 78.6% of patients achieved histo-endoscopic mucosal improvement (HEMI), a comprehensive measure combining both endoscopic improvement and histologic improvement.
- Histologic criteria for healing included: neutrophil infiltration in less than 5% of crypts, absence of crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system.
These outcomes are particularly significant because endoscopic remission and mucosal healing are associated with reduced flare-ups, decreased need for future surgical interventions, and improved long-term quality of life outcomes in ulcerative colitis patients.
Mechanism of Action: Dual-Acting IL-23 Blockade
TREMFYA represents a novel approach to inflammatory bowel disease treatment through its unique dual-acting mechanism of action. The drug is the first fully-human monoclonal antibody designed to:
- Block IL-23 p19 subunit: This action neutralizes interleukin-23 (IL-23), a key cytokine produced by activated monocytes, macrophages, and dendritic cells that drives the inflammatory cascade in ulcerative colitis.
- Bind to CD64 receptor: TREMFYA also binds to CD64, a receptor present on cells that produce IL-23, potentially providing additional immune modulation at the source of inflammation.
The IL-23 pathway represents a fundamental driver of immune-mediated inflammatory diseases, making blockade of this pathway an attractive therapeutic target. By targeting inflammation at the cellular source, TREMFYA offers a mechanistically distinct approach to managing ulcerative colitis compared to earlier TNF-inhibitor-based therapies.
Safety Profile and Tolerability
A critical component of the QUASAR findings relates to the safety and tolerability of long-term TREMFYA treatment. The data demonstrated:
- No new safety concerns were identified during the extended three-year treatment period.
- High patient retention (approximately 89%) through Week 140, suggesting favorable tolerability in real-world application.
- Consistent safety profile regardless of prior biologic and/or JAK inhibitor exposure, indicating consistent tolerability across treatment-experienced populations.
The most commonly reported adverse events from the broader TREMFYA clinical program include respiratory tract infections, headache, injection site reactions, joint pain (arthralgia), and gastrointestinal symptoms such as diarrhea and gastroenteritis. These side effect profiles are manageable and comparable to other biologic therapies used in inflammatory bowel disease treatment.
Clinical Significance for Treatment-Experienced Patients
A particularly important finding was the demonstration that efficacy was sustained regardless of patients’ prior biologic and/or JAK inhibitor treatment history. This observation has significant implications for clinical practice:
- Patients who have failed or become intolerant to multiple prior biologic agents remain candidates for TREMFYA therapy
- The consistent efficacy across treatment-experienced populations suggests that TREMFYA represents a viable option for difficult-to-treat UC cases
- The mechanism of action (IL-23 blockade) provides a distinct therapeutic approach from TNF inhibitors and vedolizumab, reducing the likelihood of cross-class resistance
Ulcerative colitis is a lifelong condition that can significantly impact patients’ overall health and they need treatment options that remain effective and well-tolerated over time. The QUASAR long-term study shows the sustained ability of TREMFYA to deliver durable results, with consistent outcomes regardless of previous biologic or JAK inhibitor treatment. With high study retention and no new safety concerns over this extended time period, the data strengthen confidence in the long-term use of TREMFYA in ulcerative colitis.
Dr. Laurent Peyrin-Biroulet
Regulatory Approvals and Clinical Availability
TREMFYA has received comprehensive regulatory approval for ulcerative colitis treatment across major markets:
United States (FDA Approval):
- Approved for adults with moderately to severely active ulcerative colitis.
- Available in both subcutaneous (SC) and intravenous (IV) induction options.
European Union (European Commission Approval):
- Approved for adult patients with moderately to severely active ulcerative colitis.
- Currently administered via IV induction regimen followed by SC maintenance therapy.
Additional Indications:
- TREMFYA is also approved in the U.S. for moderate-to-severe plaque psoriasis (adults and children 6+ years, weighing ≥88 pounds/40 kg).
- Approved for active psoriatic arthritis (adults and children 6+ years, weighing ≥88 pounds/40 kg).
- Approved for moderately to severely active Crohn’s disease (adults).
QUASAR Study Design and Methodology
The QUASAR program represents one of the most comprehensive clinical evaluations of TREMFYA in ulcerative colitis, structured in three distinct phases:
Phase 2b Dose-Ranging Induction Study:
- Evaluated multiple dosing regimens to determine optimal efficacy and safety.
- Informed selection of doses for confirmatory Phase 3 testing.
Phase 3 Confirmatory Induction Study:
- Randomized, double-blind, placebo-controlled design.
- IV induction dosing: TREMFYA 200 mg or placebo at Weeks 0, 4, and 8.
- Evaluated clinical response and remission endpoints.
Phase 3 Randomized Withdrawal Maintenance Study:
- SC maintenance regimen: TREMFYA 200 mg every 4 weeks (q4w) or 100 mg every 8 weeks (q8w) versus placebo.
- Assessed the durability of response in patients achieving clinical response to induction therapy.
Phase 3 Long-Term Extension Study (Current Data):
- Extended treatment follow-up through Week 140 (approximately 3 years).
- Assessed sustained efficacy, safety, pharmacokinetics, immunogenicity, and relevant biomarkers.
- Provided real-world evidence of long-term disease control and treatment tolerability.
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