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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• 48-week endoscopic remission [Срок оценки: 48 weeks]
• 48-week histological remission [Срок оценки: 48 weeks]

Вторичные конечные точки (11)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• The Second Affiliated Hospital of Wenzhou Medical University — Wenzhou

Публикации

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• 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
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• 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

Идентификаторы

NCT: NCT07726888 · SAHoWMU-CR2025-01-232

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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