Biomarkers Are Associated With Clinical and Endoscopic Outcomes With Vedolizumab Treatment in Ulcerative Colitis
| Autor: | Anjali Jain, Siddharth Singh, Kelly D. Hester, Elisabeth Evans, Jennifer Neill, Edvelyn Webster, Parambir S. Dulai, Brigid S. Boland, John T. Chang, William J. Sandborn, Jesus Rivera-Nieves, Robert Battat, James A. Proudfoot, Ara Mairalles, Niels Vande Casteele |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Adolescent Lymphocyte Antibodies Monoclonal Humanized Gastroenterology Endoscopy Gastrointestinal Vedolizumab Young Adult 03 medical and health sciences 0302 clinical medicine Gastrointestinal Agents Interquartile range Internal medicine medicine Humans Immunology and Allergy Prospective Studies Colitis Prospective cohort study business.industry Future Directions Prognosis medicine.disease Ulcerative colitis 030104 developmental biology medicine.anatomical_structure Monoclonal Biomarker (medicine) Colitis Ulcerative Female 030211 gastroenterology & hepatology business Biomarkers Follow-Up Studies medicine.drug |
| Zdroj: | Inflammatory Bowel Diseases. 25:410-420 |
| ISSN: | 1536-4844 1078-0998 |
| Popis: | BACKGROUND: Vedolizumab inhibits α4β7-mediated lymphocyte trafficking and is effective in ulcerative colitis (UC). This study evaluated drug and biomarker concentrations and patient outcomes during vedolizumab treatment in UC. METHODS: Prospectively scored maintenance clinical (26.5 weeks; interquartile range [IQR], 16.3–37.0 weeks) and endoscopic (23.5 weeks; IQR, 16.8–35.6 weeks) outcomes were compared with serum vedolizumab concentrations, antivedolizumab antibodies, and serum biomarkers at baseline and weeks 2, 6, 14, and 26. A linear mixed-effects model compared biomarker trajectories over time between clinical and endoscopic remitters and nonremitters. RESULTS: Thirty-two patients were included. Soluble (s)–tumor necrosis factor (TNF)–α, s-α4β7, s-mucosal addressin cell adhesion molecule (s-MAdCAM-1), and s-amyloid A (s-AA) significantly changed with treatment. A linear mixed-effects model demonstrated that s-α4β7 (P = 0.044) increased and s-MAdCAM-1 (P = 0.006) and s-vascular cell adhesion molecule-1 (s-VCAM-1, P = 0.001) decreased more rapidly in patients achieving clinical remission in maintenance. S-MAdCAM-1 (P = 0.005), s-intracellular adhesion molecule-1 (ICAM-1; P = 0.014), s-VCAM-1 (P < 0.001), and s-TNF (P = 0.052) decreased more rapidly in endoscopic remitters. In clinical remitters, higher week 14 (20.3 ng/mL vs 6.0 ng/mL; P = 0.013) and week 26 (14.1 ng/mL vs 8.6 ng/mL; P = 0.05) s-α4β7 were observed. In endoscopic remitters, week 2 (6.7 pg/mL vs 17.8 pg/mL; P = 0.038) and week 6 (3.9 pg/mL vs 15.6 pg/mL; P = 0.005) s-TNF and week 14 s-VCAM (589.1 ng/mL vs 746.0 ng/mL; P = 0.05) were lower. CONCLUSION: Serum biomarkers were associated with outcomes in vedolizumab-treated UC patients. s-α4β7 increased, whereas s-MAdCAM-1, s-VCAM-1, s-ICAM-1, and s-TNF decreased more rapidly in remitters. At individual time points, induction s-TNF and maintenance s-VCAM-1 concentrations were lower, whereas maintenance s-α4β7 concentrations were higher in remitters. |
| Databáze: | OpenAIRE |
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