Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis.
Calprotectin
Cytokines
Diagnostic odds ratio
Robarts histopathology index
antiTNF
Journal
BMC gastroenterology
ISSN: 1471-230X
Titre abrégé: BMC Gastroenterol
Pays: England
ID NLM: 100968547
Informations de publication
Date de publication:
02 Oct 2020
02 Oct 2020
Historique:
received:
22
04
2020
accepted:
09
09
2020
entrez:
3
10
2020
pubmed:
4
10
2020
medline:
15
5
2021
Statut:
epublish
Résumé
There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis. Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004 to 2014, followed by a validation study from 2014 to 2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts. We included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54. The combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.
Sections du résumé
BACKGROUND
BACKGROUND
There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis.
METHODS
METHODS
Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004 to 2014, followed by a validation study from 2014 to 2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts.
RESULTS
RESULTS
We included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54.
CONCLUSIONS
CONCLUSIONS
The combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.
Identifiants
pubmed: 33008302
doi: 10.1186/s12876-020-01447-0
pii: 10.1186/s12876-020-01447-0
pmc: PMC7532085
doi:
Substances chimiques
Biomarkers
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
321Subventions
Organisme : Helse Nord RHF
ID : SFP-50-04
Organisme : Helse Nord RHF
ID : SFP-888-09
Organisme : Helse Nord RHF
ID : SFP-1136-13
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