Gene Expression Signature for Prediction of Golimumab Response in a Phase 2a Open-Label Trial of Patients With Ulcerative Colitis
| Autor: | Hongyan Zhang, Timothy Davison, S Plevy, Laura Knight, Abhijit Mazumder, Jewel Johanns, Katherine Li, William J. Sandborn, Shannon Telesco, Corey A. Siegel, Paul Rutgeerts, Sian Dibben, Richard Strauss, Bethany Paxson, Frédéric Baribaud, Mark Curran, Walter Reinisch, Carrie Brodmerkel, Stefan Schreiber, Lilianne Lee-Lian Kim, Linda E. Greenbaum |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetic Markers medicine.medical_specialty Necrosis Time Factors Colon Clinical Decision-Making Anti-Inflammatory Agents Gastroenterology Inflammatory bowel disease Severity of Illness Index 03 medical and health sciences 0302 clinical medicine Gastrointestinal Agents Predictive Value of Tests Internal medicine Statistical significance medicine Humans Prospective Studies Intestinal Mucosa Precision Medicine Wound Healing Hepatology business.industry Gene Expression Profiling Remission Induction Antibodies Monoclonal Gene signature medicine.disease Ulcerative colitis Infliximab Golimumab 030104 developmental biology Treatment Outcome ROC Curve Pharmacogenetics Area Under Curve 030211 gastroenterology & hepatology Tumor necrosis factor alpha Colitis Ulcerative medicine.symptom Inflammation Mediators business Transcriptome medicine.drug |
| Zdroj: | Gastroenterology. 155(4) |
| ISSN: | 1528-0012 |
| Popis: | Golimumab, a tumor necrosis factor antagonist, is an effective treatment for patients with moderate-to-severe ulcerative colitis (UC); however, more than 50% of initial responders lose their response to the drug within the first year of therapy. A gene expression signature identified in colon biopsies collected before treatment was associated with response to infliximab, and was subsequently refined to associate with mucosal healing in response to golimumab. We performed a phase 2a open-label study of 103 golimumab-treated patients with moderate-to-severe UC to test whether the baseline gene expression signature could be used to predict which patients would achieve mucosal healing, clinical response, and clinical remission at weeks 6 and 30 of treatment. The gene expression signature identified patients who went on to achieve mucosal healing at treatment week 6 with an area under the receiver operating characteristic curve (AUCROC) of 0.688 (P = .002) and at week 30 with an AUCROC of 0.671 (P = .006). The signature identified patients with mucosal healing with 87% sensitivity, but only 34% specificity, limiting its clinical utility. The baseline gene expression signature did not identify patients who went on to achieve clinical remission or clinical response with statistical significance. Further studies are needed to identify biomarkers that can be used to predict which patients with UC will respond to treatment with anti–tumor necrosis factor agents. ClinicalTrials.gov no: NCT01988961 . |
| Databáze: | OpenAIRE |
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