Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep;39(9):2553-2562.
doi: 10.1007/s10067-020-05030-6. Epub 2020 Mar 24.

Fetuin-A and thyroxin binding globulin predict rituximab response in rheumatoid arthritis patients with insufficient response to anti-TNFα

Minh Vu Chuong Nguyen  1   2 , Anaïs Courtier  3 , Annie Adrait  4 , Federica Defendi  5 , Yohann Couté  4 , Athan Baillet  6   7 , Lisa Guigue  3 , Jacques-Eric Gottenberg  8 , Chantal Dumestre-Pérard  5 , Virginie Brun  4 , Philippe Gaudin  6   7
Affiliations

Fetuin-A and thyroxin binding globulin predict rituximab response in rheumatoid arthritis patients with insufficient response to anti-TNFα

Minh Vu Chuong Nguyen et al. Clin Rheumatol. 2020 Sep.

Abstract

Objectives: 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.

Methods: 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).

Results: 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%.

Conclusion: 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.

Keywords: Biomarkers; Fetuin-A; Prediction; Rheumatoid arthritis; Rituximab; TNF inhibitors; Thyroxin binding globulin; bDMARD.

PubMed Disclaimer

References

    1. Maillefert JF, Combe B, Goupille P, Cantagrel A, Dougados M (2003) Long term structural effects of combination therapy in patients with early rheumatoid arthritis: five year follow up of a prospective double blind controlled study. Ann Rheum Dis 62:764–766 - DOI
    1. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN, Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 343:1594–1602. https://doi.org/10.1056/NEJM200011303432202 - DOI - PubMed
    1. Navarro-Millán I, Curtis JR (2013) Newest clinical trial results with antitumor necrosis factor and nonantitumor necrosis factor biologics for rheumatoid arthritis. Curr Opin Rheumatol 25:384–390. https://doi.org/10.1097/BOR.0b013e32835fc62e - DOI - PubMed - PMC
    1. Favalli EG, Raimondo MG, Becciolini A, Crotti C, Biggioggero M, Caporali R (2017) The management of first-line biologic therapy failures in rheumatoid arthritis: current practice and future perspectives. Autoimmun Rev 16:1185–1195. https://doi.org/10.1016/j.autrev.2017.10.002 - DOI - PubMed
    1. Gottenberg J-E, Brocq O, Perdriger A, Lassoued S, Berthelot JM, Wendling D, Euller-Ziegler L, Soubrier M, Richez C, Fautrel B, Constantin AL, Mariette X, Morel J, Gilson M, Cormier G, Salmon JH, Rist S, Lioté F, Marotte H, Bonnet C, Marcelli C, Sellam J, Meyer O, Solau-Gervais E, Guis S, Ziza JM, Zarnitsky C, Chary-Valckenaere I, Vittecoq O, Saraux A, Pers YM, Gayraud M, Bolla G, Claudepierre P, Ardizzone M, Dernis E, Breban MA, Fain O, Balblanc JC, Aberkane O, Vazel M, Back C, Candon S, Chatenoud L, Perrodeau E, Sibilia J, Ravaud P (2016) Non-TNF-targeted biologic vs a second anti-TNF drug to treat rheumatoid arthritis in patients with insufficient response to a first anti-TNF drug: a randomized clinical trial. JAMA 316:1172–1180. https://doi.org/10.1001/jama.2016.13512 - DOI - PubMed

MeSH terms

Associated data

LinkOut - more resources