Fetuin-A and thyroxin binding globulin predict rituximab response in rheumatoid arthritis patients with insufficient response to anti-TNFα.
Biomarkers
Fetuin-A
Prediction
Rheumatoid arthritis
Rituximab
TNF inhibitors
Thyroxin binding globulin
bDMARD
Journal
Clinical rheumatology
ISSN: 1434-9949
Titre abrégé: Clin Rheumatol
Pays: Germany
ID NLM: 8211469
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
25
11
2019
accepted:
05
03
2020
revised:
07
02
2020
pubmed:
27
3
2020
medline:
15
5
2021
entrez:
27
3
2020
Statut:
ppublish
Résumé
Rheumatoid arthritis (RA) is a debilitating disease, but patient management and treatment have been revolutionized since the advent of bDMARDs. However, about one third of RA patients do not respond to specific bDMARD treatment without clear identified reasons. Different bDMARDs must be tried until the right drug is found. Here, we sought to identify a predictive protein signature to stratify patient responsiveness to rituximab (RTX) among patients with an insufficient response to a first anti-TNFα treatment. Serum samples were collected at baseline before RTX initiation. A proteomics study comparing responders and nonresponders was conducted to identify and select potential predictive biomarkers whose concentration was measured by quantitative assays. Logistic regression was performed to determine the best biomarker combination to predict good or nonresponse to RTX (EULAR criteria after 6 months' treatment). Eleven biomarkers potentially discriminating between responders and nonresponders were selected following discovery proteomics. Quantitative immunoassays and univariate statistical analysis showed that fetuin-A and thyroxine binding globulin (TBG) presented a good capacity to discriminate between patient groups. A logistic regression analysis revealed that the combination of fetuin-A plus TBG could accurately predict a patient's responsiveness to RTX with an AUC of 0.86, sensitivity of 80%, and a specificity of 79%. In RA patients for whom a first anti-TNFα treatment has failed, the serum abundance of fetuin-A and TBG before initiating RTX treatment is an indicator for their response status at 6 months. ClinicalTrials.gov identifier: NCT01000441. Key Points • Proteomic analysis revealed 11 putative predictive biomarkers to discriminate rituximab responder vs. nonresponder RA patients. • Fetuin-A and TBG are significantly differentially expressed at baseline in rituximab responder vs. nonresponder RA patients. • Algorithm combining fetuin-A and TBG accurately predicts response to rituximab in RA patients with insufficient response to TNFi.
Identifiants
pubmed: 32212002
doi: 10.1007/s10067-020-05030-6
pii: 10.1007/s10067-020-05030-6
doi:
Substances chimiques
Antirheumatic Agents
0
Thyroxine-Binding Globulin
0
alpha-2-HS-Glycoprotein
0
Rituximab
4F4X42SYQ6
Thyroxine
Q51BO43MG4
Banques de données
ClinicalTrials.gov
['NCT01000441']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2553-2562Subventions
Organisme : Investissement d'Avenir Infrastructures Nationales en Biologie et Santé
ID : ANR-10-INBS-08
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