Validation in the ESPOIR cohort of vitamin K-dependent protein S (PROS) as a potential biomarker capable of predicting response to the methotrexate/etanercept combination.
Adalimumab
Biomarker
CO7
Etanercept
PROS
Prediction
Response
Rheumatoid arthritis
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
21 03 2022
21 03 2022
Historique:
received:
24
01
2022
accepted:
24
02
2022
entrez:
22
3
2022
pubmed:
23
3
2022
medline:
6
5
2022
Statut:
epublish
Résumé
To validate the ability of PROS (vitamin K-dependent protein S) and CO7 (complement component C7) to predict response to the methotrexate (MTX)/etanercept (ETA) combination in rheumatoid arthritis (RA) patients who received this therapeutic combination in a well-documented cohort. From the ESPOIR cohort, RA patients having received the MTX/ETA or MTX/adalimumab (ADA) combination as a first-line biologic treatment were included. Serum concentrations of PROS and CO7 were measured by ELISA prior to the initiation of ETA or ADA, at a time where the disease was active (DAS28 ESR > 3.2). The clinical efficacy (response/non-response) of both combinations has been evaluated after at least 6 months of treatment, according to the EULAR response criteria with some modifications. Thirty-two were treated by MTX/ETA; the numbers of responders and non-responders were 24 and 8, respectively. Thirty-three patients received the MTX/ADA combination; 27 and 5 patients were respectively responders and non-responders. While there were no differences for demographic, clinical, biological, and X-rays data, as well as for CO7, serum levels of PROS tended to be significantly higher in responders to the MTX/ETA combination (p = 0.08) while no difference was observed in the group receiving MTX/ADA. For PROS, the best concentration threshold to differentiate both groups was calculated at 40 μg/ml using ROC curve. The theranostic performances of PROS appeared better for the ETA/MTX combination. When considering the response to this combination, analysis of pooled data from ESPOIR and SATRAPE (initially used to validate PROS and CO7 as potential theranostic biomarkers) cohorts led to a higher theranostic value of PROS that became significant (p = 0.009). PROS might be one candidate of a combination of biomarkers capable of predicting the response to MTX/ETA combination in RA patients refractory to MTX. ClinicalTrials.gov identifiers: NCT03666091 and NCT00234234 .
Sections du résumé
BACKGROUND
To validate the ability of PROS (vitamin K-dependent protein S) and CO7 (complement component C7) to predict response to the methotrexate (MTX)/etanercept (ETA) combination in rheumatoid arthritis (RA) patients who received this therapeutic combination in a well-documented cohort.
METHOD
From the ESPOIR cohort, RA patients having received the MTX/ETA or MTX/adalimumab (ADA) combination as a first-line biologic treatment were included. Serum concentrations of PROS and CO7 were measured by ELISA prior to the initiation of ETA or ADA, at a time where the disease was active (DAS28 ESR > 3.2). The clinical efficacy (response/non-response) of both combinations has been evaluated after at least 6 months of treatment, according to the EULAR response criteria with some modifications.
RESULTS
Thirty-two were treated by MTX/ETA; the numbers of responders and non-responders were 24 and 8, respectively. Thirty-three patients received the MTX/ADA combination; 27 and 5 patients were respectively responders and non-responders. While there were no differences for demographic, clinical, biological, and X-rays data, as well as for CO7, serum levels of PROS tended to be significantly higher in responders to the MTX/ETA combination (p = 0.08) while no difference was observed in the group receiving MTX/ADA. For PROS, the best concentration threshold to differentiate both groups was calculated at 40 μg/ml using ROC curve. The theranostic performances of PROS appeared better for the ETA/MTX combination. When considering the response to this combination, analysis of pooled data from ESPOIR and SATRAPE (initially used to validate PROS and CO7 as potential theranostic biomarkers) cohorts led to a higher theranostic value of PROS that became significant (p = 0.009).
CONCLUSION
PROS might be one candidate of a combination of biomarkers capable of predicting the response to MTX/ETA combination in RA patients refractory to MTX.
TRIAL REGISTRATION
ClinicalTrials.gov identifiers: NCT03666091 and NCT00234234 .
Identifiants
pubmed: 35313956
doi: 10.1186/s13075-022-02762-5
pii: 10.1186/s13075-022-02762-5
pmc: PMC8935769
doi:
Substances chimiques
Antirheumatic Agents
0
Biomarkers
0
Protein S
0
Adalimumab
FYS6T7F842
Etanercept
OP401G7OJC
Methotrexate
YL5FZ2Y5U1
Banques de données
ClinicalTrials.gov
['NCT00234234', 'NCT03666091']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
72Informations de copyright
© 2022. The Author(s).
Références
PLoS One. 2014 Dec 29;9(12):e115800
pubmed: 25546405
Health Technol Assess. 2018 Nov;22(66):1-294
pubmed: 30501821
Arthritis Res Ther. 2015 Mar 06;17:45
pubmed: 25884688
Joint Bone Spine. 2019 Mar;86(2):195-201
pubmed: 29885551
Arthritis Rheumatol. 2021 Feb;73(2):212-222
pubmed: 32909363
Arthritis Rheumatol. 2016 Jun;68(6):1346-52
pubmed: 26815727
Joint Bone Spine. 2015 Jan;82(1):13-7
pubmed: 25238951
Rheumatology (Oxford). 2017 Jun 1;56(6):1019-1024
pubmed: 28096457
Arthritis Res Ther. 2021 Sep 18;23(1):245
pubmed: 34537057
Arthritis Res Ther. 2009;11(3):R76
pubmed: 19460157
Arthritis Rheumatol. 2019 Dec;71(12):1987-1996
pubmed: 31342661
Ann Rheum Dis. 2009 Aug;68(8):1328-33
pubmed: 18664547
Clin Exp Immunol. 2008 Aug;153(2):188-95
pubmed: 18549443
Theranostics. 2015 Aug 09;5(11):1214-24
pubmed: 26379787
Arthritis Rheum. 2010 Sep;62(9):2569-81
pubmed: 20872595
Joint Bone Spine. 2019 Mar;86(2):151-158
pubmed: 29981377