Efficacy and Safety of Guselkumab in Patients With Moderate-to-Severe Ulcerative Colitis

Official title

Efficacy and Safety of Guselkumab in Patients With Moderate-to-Severe Ulcerative Colitis:A Real-World Prospective Cohort Study.

Overview

In a real-world setting, this study systematically evaluates the clinical efficacy and safety of guselkumab (GUS) in the treatment of ulcerative colitis (UC), encompassing multi-dimensional outcomes including clinical remission, biochemical remission, endoscopic remission, histologic healing, and intestinal ultrasound changes.

Interventions

• Drug Guselkumab
  All the patients receive GUS (IV) 200 mg induction therapy at weeks 0, 4, and 8, and who met the criteria for clinical symptom remission, biochemical remission, and improvement in intestinal ultrasound based on the clinical assessment at week 12, proceeded to receive GUS (SC) 100 mg every 8 weeks as maintenance therapy. Patients who did not meet the above criteria received GUS (SC) 200 mg every 4 weeks as maintenance therapy. At week 24, based on clinical and endoscopic evaluations, patients who

Primary outcome measures

• 48-week endoscopic remission [Time frame: 48 weeks]
• 48-week histological remission [Time frame: 48 weeks]

Secondary outcome measures (11)

• 12-week clinical remission [Time frame: 12 weeks]
• 12-week biochemical remission [Time frame: 12 weeks]
• 12-week intestinal ultrasound response [Time frame: 12 weeks]
• 24-week and 48-week intestinal ultrasound response [Time frame: 24 weeks; 48 weeks]
• 24-week endoscopic response and remission [Time frame: 24 weeks]
• 24-week and 48-week Corticosteroid-free remission rate [Time frame: 24 weeks; 48 weeks]
• 48-week drug persistence rate [Time frame: 48 weeks]
• Hospitalization and surgery rates at week 48 [Time frame: 48 weeks]
• Impact of Prior Biologic Exposure on Efficacy [Time frame: Efficacy comparisons were compared at all key study visits: baseline, week 12, week 24, and week 48.]
• Inflammatory Bowel Disease Questionnaire (IBD-Q) scores at week 48 [Time frame: 48 weeks]
• Exploratory Study (Comparing the Efficacy of GUS and VDZ) [Time frame: Efficacy comparisons were compared at all key study visits: baseline, week 12, week 24, and week 48]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years.
• Diagnosis of ulcerative colitis is established based on clinical manifestations, laboratory findings, colonoscopy, radiological imaging (CT or ultrasound), and histopathological examination.
• Presence of moderate-to-severe disease activity, defined as a modified Mayo score (MMS) ≥ 5 points, accompanied by a rectal bleeding subscore (RBS) ≥ 1 and a Mayo endoscopic subscore (MES) ≥ 2.
• Inadequate response or intolerance to at least one conventional therapy (5-aminosalicylates, corticosteroids, or immunosuppressants), as assessed by the investigator according to clinical practice.
• Based on the research cohort requirements, the GUS real-world cohort may include patients who are biologic-naive, have failed first-line therapy, or have failed multiple lines of therapy.
• Availability of baseline data for disease activity assessment, including symptom scores (partial Mayo score or PRO2), endoscopic evaluation (MES), biochemical markers (C-reactive protein or fecal calprotectin), or imaging parameters (CT or intestinal ultrasonography).
• Patients enrolled in the prospective GUS cohort are required to provide written informed consent voluntarily.

Exclusion criteria

• Diagnosed with other intestinal diseases, such as Crohn's disease, intestinal tuberculosis, infectious colitis, ischemic colitis or other chronic intestinal inflammatory diseases;
• If there is an active intestinal infection, and the fecal culture or pathogen test shows positive within 8 weeks before the study (including Clostridium difficile, cytomegalovirus, etc.), and the re-examination turns negative without any signs of persistent infection, a re-evaluation can be conducted.
• Combined with severe infections, malignant tumors, severe liver and kidney dysfunction, or accompanied by active autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, and Graves' disease that may interfere with disease assessment
• Those who have undergone total colorectal resection or stoma surgery in the past and whose disease activity cannot be evaluated, or are expected to undergo major intestinal surgery during the study period;
• Has had a severe allergic reaction to monoclonal antibodies;
• During pregnancy or lactation (can be recorded as an independent cohort but not included in the primary analysis);
• Severe absence of baseline and follow-up data makes it impossible to determine efficacy or safety.
• Currently participating in other interventional clinical trials that may interfere with the results of this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• The Second Affiliated Hospital of Wenzhou Medical University — Wenzhou

Publications

• Ilvemark JFKF, Hansen T, Goodsall TM, Seidelin JB, Al-Farhan H, Allocca M, Begun J, Bryant RV, Carter D, Christensen B, Dubinsky MC, Gecse KB, Kucharzik T, Lu C, Maaser C, Maconi G, Nylund K, Palmela C, Wilson SR, Novak K, Wilkens R. Defining Transabdominal Intestinal Ultrasound Treatment Response and Remission in Inflammatory Bowel Disease: Systematic Review and Expert Consensus Statement. J Croh PMID 34614172
• Kappelman MD, Adimadhyam S, Hou L, Wolfe AE, Smith S, Simon AL, Moyneur E, Reynolds JS, Toh S, Dobes A, Parlett LE, Haynes K, Selvan M, Ma Q, Nair V, Burris J, Dorand JE, Dawwas GK, Lewis JD, Long MD. Real-World Evidence Comparing Vedolizumab and Ustekinumab in Antitumor Necrosis Factor-Experienced Patients With Crohn's Disease. Am J Gastroenterol. 2023 Apr 1;118(4):674-684. doi: 10.14309/ajg.0000 PMID 36508681
• Buisson A, Serrero M, Altwegg R, Guilmoteau T, Bouguen G, Nachury M, Amiot A, Vuitton L, Treton X, Caillo L, Pereira B, Fumery M. Real-World Comparison of the Effectiveness of Tofacitinib and Ustekinumab in Patients With Ulcerative Colitis: The TORUS Study. Clin Gastroenterol Hepatol. 2026 Apr;24(4):1141-1150. doi: 10.1016/j.cgh.2025.07.044. Epub 2025 Aug 18. PMID 40835043
• Rubin DT, Allegretti JR, Panes J, Shipitofsky N, Yarandi SS, Huang KG, Germinaro M, Wilson R, Zhang H, Johanns J, Feagan BG, Hisamatsu T, Lichtenstein GR, Bressler B, Peyrin-Biroulet L, Sands BE, Dignass A; QUASAR Study Group. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies PMID 39706209
• Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, Li S, Shen YK, Gordon KB. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J PMID 28057361
• Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, Li S, Kimball AB. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017 Mar;76(3): PMID 28057360
• Verstockt B, Salas A, Sands BE, Abraham C, Leibovitzh H, Neurath MF, Vande Casteele N; Alimentiv Translational Research Consortium (ATRC). IL-12 and IL-23 pathway inhibition in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2023 Jul;20(7):433-446. doi: 10.1038/s41575-023-00768-1. Epub 2023 Apr 17. PMID 37069321
• Kapizioni C, Desoki R, Lam D, Balendran K, Al-Sulais E, Subramanian S, Rimmer JE, De La Revilla Negro J, Pavey H, Pele L, Brooks J, Moran GW, Irving PM, Limdi JK, Lamb CA; UK IBD BioResource Investigators; Parkes M, Raine T. Biologic Therapy for Inflammatory Bowel Disease: Real-World Comparative Effectiveness and Impact of Drug Sequencing in 13 222 Patients within the UK IBD BioResource. J Crohns PMID 38041850

Identifiers

NCT: NCT07726888 · SAHoWMU-CR2025-01-232

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗