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This prospective observational study is going to develop and validate a prediction model of response to biologic agents and small molecular agents for Korean patients with ulcerative colitis.
In this prospective observational study, patients with confirmed ulcerative colitis, who are going to receive vedolizumab, ustekinumab, or tofacitinib will be enrolled after an informed consent. In the screening period, inclusion/exclusion criteria will be checked and if eligible and consented, demographic data, medical history, disease characteristics and disease activity data will be collected. Before drug administration (week 0), baseline lower GI endoscopy will be performed and colon tissues will be collected. Blood sample and fecal sample will also be collected. After induction therapy with each drug, clinical and endoscopic response will be evaluated at week 14 to week 16 and patients will be classified into responders non-responders. Combing clinical data, blood laboratory data, fecal inflammatory biomarker, genetic data, and colonic transcriptomic data, a prediction model for response to induction therapy will be developed and it will be validated in another patient group. Similarly, based on evaluation at week 52, a prediction model for maintenance response will also be developed and validated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with confirmed ulcerative colitis | Patients with confirmed ulcerative colitis, who are going to receive vedolizumab therapy (n=100: development cohort n=70 and validation cohort n=30), ustekinumab therapy (n=100: development cohort n=70 and validation cohort n=30), or tofacitinib therapy (n=100: development cohort n=70 and validation cohort n=30), will be enrolled. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vedolizumab, Ustekinumab, or Tofacitinib | Drug | Drug administration and prospective follow-up for evaluating response |
|
| Measure | Description | Time Frame |
|---|---|---|
| Response to induction therapy | A decrease from baseline in the total Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1, together with Mayo endoscopic subscore of 0 to 1 | Week 14 to Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Remission to induction therapy | Full Mayo score 0 to 2 + Any component of full Mayo score of 1 or less + Mayo endoscopic subscore of 0 to 1 | Week 14 to Week 16 |
| Complete Mayo endoscopic subscore remission to induction therapy |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with an established diagnosis of ulcerative colitis and who are going to receive vedolizumab, ustekinumab, or tofacitinib will be enrolled in this study.
Patients who give a voluntary informed consent will be eligible.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Byong Duk Ye, MD, PhD | Contact | 82230103180 | bdye@amc.seoul.kr |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asan Medical Center | Recruiting | Seoul | 05505 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17653185 | Background | Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007 Jul 26;448(7152):427-34. doi: 10.1038/nature06005. | |
| 22001864 | Background | Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012 Jan;142(1):46-54.e42; quiz e30. doi: 10.1053/j.gastro.2011.10.001. Epub 2011 Oct 14. |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
Not provided
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| ID | Term |
|---|---|
| C543529 | vedolizumab |
| D000069549 | Ustekinumab |
| C479163 | tofacitinib |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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Genomic DNA, serum, feces, colon tissue
Mayo endoscopic subscore of 0
| Week 14 to Week 16 |
| Ulcerative colitis endoscopic index of severity remission to induction therapy | Ulcerative colitis endoscopic index of 0 to 1 | Week 14 to Week 16 |
| Response to maintenance therapy | A decrease from baseline in the total Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1, together with Mayo endoscopic subscore of 0 to 1 | Week 52 |
| Remission to maintenance therapy | Full Mayo score 0 to 2 + Any component of full Mayo score of 1 or less + Mayo endoscopic subscore of 0 to 1 | Week 52 |
| Complete Mayo endoscopic subscore remission to maintenance therapy | Mayo endoscopic subscore of 0 | Week 52 |
| Ulcerative colitis endoscopic index of severity remission to maintenance therapy | Ulcerative colitis endoscopic index of 0 to 1 | Week 52 |
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| 16339095 | Background | Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. |
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| 31092589 | Background | Schleier L, Wiendl M, Heidbreder K, Binder MT, Atreya R, Rath T, Becker E, Schulz-Kuhnt A, Stahl A, Schulze LL, Ullrich K, Merz SF, Bornemann L, Gunzer M, Watson AJM, Neufert C, Atreya I, Neurath MF, Zundler S. Non-classical monocyte homing to the gut via alpha4beta7 integrin mediates macrophage-dependent intestinal wound healing. Gut. 2020 Feb;69(2):252-263. doi: 10.1136/gutjnl-2018-316772. Epub 2019 May 15. |
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| 32601912 | Background | Bandres-Ciga S, Saez-Atienzar S, Kim JJ, Makarious MB, Faghri F, Diez-Fairen M, Iwaki H, Leonard H, Botia J, Ryten M, Hernandez D, Gibbs JR, Ding J, Gan-Or Z, Noyce A, Pihlstrom L, Torkamani A, Soltis AR, Dalgard CL; American Genome Center; Scholz SW, Traynor BJ, Ehrlich D, Scherzer CR, Bookman M, Cookson M, Blauwendraat C, Nalls MA, Singleton AB; International Parkinson Disease Genomics Consortium. Large-scale pathway specific polygenic risk and transcriptomic community network analysis identifies novel functional pathways in Parkinson disease. Acta Neuropathol. 2020 Sep;140(3):341-358. doi: 10.1007/s00401-020-02181-3. Epub 2020 Jun 29. |
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| D015212 |
| Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |