Cargando…
Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up
INTRODUCTION: The development of biomarkers to guide management of anti–tumor necrosis factor (TNF) agents in patients with inflammatory bowel disease (IBD) is an unmet need. We developed an in vitro blood assay to predict patient long-term outcome with the anti-TNFα agent infliximab (IFX). METHODS:...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886452/ https://www.ncbi.nlm.nih.gov/pubmed/33735154 http://dx.doi.org/10.14309/ctg.0000000000000298 |
_version_ | 1783651796961460224 |
---|---|
author | Bravo, Francisco Macpherson, Jamie A. Slack, Emma Patuto, Nicolas Cahenzli, Julia McCoy, Kathy D. Macpherson, Andrew J. Juillerat, Pascal |
author_facet | Bravo, Francisco Macpherson, Jamie A. Slack, Emma Patuto, Nicolas Cahenzli, Julia McCoy, Kathy D. Macpherson, Andrew J. Juillerat, Pascal |
author_sort | Bravo, Francisco |
collection | PubMed |
description | INTRODUCTION: The development of biomarkers to guide management of anti–tumor necrosis factor (TNF) agents in patients with inflammatory bowel disease (IBD) is an unmet need. We developed an in vitro blood assay to predict patient long-term outcome with the anti-TNFα agent infliximab (IFX). METHODS: Patients with IBD were classified according to the shedding of an L-selectin (CD62L) from the surface of their granulocytes in whole blood. CD62L shedding was quantified by flow cytometry before and after drug administration. A clinical data collection from June 2012 to August 2017 with blinded IFX management was aimed at validating the long-term predictive value of this test. RESULTS: Among 33 patients with IBD (17 Crohn's disease and 5 ulcerative colitis), 22 were predicted functional responders (PFR) and 11 were predicted as nonresponders (NR) according to the in vitro test. Five years after study initiation, 72% of PFR were still treated with IFX (vs 27% in the NR group; P < 0.05), with a median time spent under IFX of 45 vs 12 months (P = 0.019), respectively. Thirty-five medicosurgical events occurred with a median time to first event of 3 vs 30 months (P = 0.023), respectively. Our assay was the best independent predictor of staying long term on IFX (P = 0.056). DISCUSSION: An assay-based in vitro test for functional blockade of TNFα (CD62L shedding) provides an excellent long-term (at 3–5 years) independent predictor of durable use of IFX in patients with IBD. Testing patients could personalize decision making to significantly reduce costs and risk of adverse events and complications. [Image: see text] |
format | Online Article Text |
id | pubmed-7886452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Wolters Kluwer |
record_format | MEDLINE/PubMed |
spelling | pubmed-78864522021-02-17 Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up Bravo, Francisco Macpherson, Jamie A. Slack, Emma Patuto, Nicolas Cahenzli, Julia McCoy, Kathy D. Macpherson, Andrew J. Juillerat, Pascal Clin Transl Gastroenterol Article INTRODUCTION: The development of biomarkers to guide management of anti–tumor necrosis factor (TNF) agents in patients with inflammatory bowel disease (IBD) is an unmet need. We developed an in vitro blood assay to predict patient long-term outcome with the anti-TNFα agent infliximab (IFX). METHODS: Patients with IBD were classified according to the shedding of an L-selectin (CD62L) from the surface of their granulocytes in whole blood. CD62L shedding was quantified by flow cytometry before and after drug administration. A clinical data collection from June 2012 to August 2017 with blinded IFX management was aimed at validating the long-term predictive value of this test. RESULTS: Among 33 patients with IBD (17 Crohn's disease and 5 ulcerative colitis), 22 were predicted functional responders (PFR) and 11 were predicted as nonresponders (NR) according to the in vitro test. Five years after study initiation, 72% of PFR were still treated with IFX (vs 27% in the NR group; P < 0.05), with a median time spent under IFX of 45 vs 12 months (P = 0.019), respectively. Thirty-five medicosurgical events occurred with a median time to first event of 3 vs 30 months (P = 0.023), respectively. Our assay was the best independent predictor of staying long term on IFX (P = 0.056). DISCUSSION: An assay-based in vitro test for functional blockade of TNFα (CD62L shedding) provides an excellent long-term (at 3–5 years) independent predictor of durable use of IFX in patients with IBD. Testing patients could personalize decision making to significantly reduce costs and risk of adverse events and complications. [Image: see text] Wolters Kluwer 2021-02-15 /pmc/articles/PMC7886452/ /pubmed/33735154 http://dx.doi.org/10.14309/ctg.0000000000000298 Text en © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Bravo, Francisco Macpherson, Jamie A. Slack, Emma Patuto, Nicolas Cahenzli, Julia McCoy, Kathy D. Macpherson, Andrew J. Juillerat, Pascal Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up |
title | Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up |
title_full | Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up |
title_fullStr | Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up |
title_full_unstemmed | Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up |
title_short | Prospective Validation of CD-62L (L-Selectin) as Marker of Durable Response to Infliximab Treatment in Patients With Inflammatory Bowel Disease: A 5-Year Clinical Follow-up |
title_sort | prospective validation of cd-62l (l-selectin) as marker of durable response to infliximab treatment in patients with inflammatory bowel disease: a 5-year clinical follow-up |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886452/ https://www.ncbi.nlm.nih.gov/pubmed/33735154 http://dx.doi.org/10.14309/ctg.0000000000000298 |
work_keys_str_mv | AT bravofrancisco prospectivevalidationofcd62llselectinasmarkerofdurableresponsetoinfliximabtreatmentinpatientswithinflammatoryboweldiseasea5yearclinicalfollowup AT macphersonjamiea prospectivevalidationofcd62llselectinasmarkerofdurableresponsetoinfliximabtreatmentinpatientswithinflammatoryboweldiseasea5yearclinicalfollowup AT slackemma prospectivevalidationofcd62llselectinasmarkerofdurableresponsetoinfliximabtreatmentinpatientswithinflammatoryboweldiseasea5yearclinicalfollowup AT patutonicolas prospectivevalidationofcd62llselectinasmarkerofdurableresponsetoinfliximabtreatmentinpatientswithinflammatoryboweldiseasea5yearclinicalfollowup AT cahenzlijulia prospectivevalidationofcd62llselectinasmarkerofdurableresponsetoinfliximabtreatmentinpatientswithinflammatoryboweldiseasea5yearclinicalfollowup AT mccoykathyd prospectivevalidationofcd62llselectinasmarkerofdurableresponsetoinfliximabtreatmentinpatientswithinflammatoryboweldiseasea5yearclinicalfollowup AT macphersonandrewj prospectivevalidationofcd62llselectinasmarkerofdurableresponsetoinfliximabtreatmentinpatientswithinflammatoryboweldiseasea5yearclinicalfollowup AT juilleratpascal prospectivevalidationofcd62llselectinasmarkerofdurableresponsetoinfliximabtreatmentinpatientswithinflammatoryboweldiseasea5yearclinicalfollowup |