Oliver, J, Nair, N, Orozco, G et al. (8 more authors) (2021) Transcriptome-wide study of TNF-inhibitor therapy in rheumatoid arthritis reveals early signature of successful treatment. Arthritis Research & Therapy, 23 (1). 80. ISSN 1478-6354
Abstract
Background
Despite the success of TNF-inhibitor therapy in rheumatoid arthritis treatment, up to 40% of patients fail to respond adequately. This study aimed to identify transcriptome-based biomarkers of adalimumab response in rheumatoid arthritis (RA) to aid timely switching in non-responder patients and provide a better mechanistic understanding of the pathways involved in response/non-response.
Methods
The Affymetrix Human Transcriptome Array 2.0 (HTA) was used to measure the transcriptome in whole blood at pre-treatment and at 3 months in EULAR good- and non-responders to adalimumab therapy. Differential expression of transcripts was analysed at the transcript level using multiple linear regression. Differentially expressed genes were validated in independent samples using OpenArray™ RT-qPCR.
Results
In total, 813 transcripts were differentially expressed between pre-treatment and 3 months in adalimumab good-responders. No significant differential expression was observed between good- and non-responders at either time-point and no significant changes were observed in non-responders between time-points. OpenArray™ RT-qPCR was performed for 104 differentially expressed transcripts in good-responders, selected based on magnitude of effect or p value or based on prior association with RA or the immune system, validating differential expression for 17 transcripts.
Conclusions
An early transcriptome signature of DAS28 response to adalimumab has been identified and replicated in independent datasets. Whilst treat-to-target approaches encourage early switching in non-responsive patients, registry evidence suggests that this does not always occur. The results herein could guide the development of a blood test to distinguish responders from non-responders at 3 months and support clinical decisions to switch non-responsive patients to an alternative therapy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s). 2021. This is an open access article under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | TNF-inhibitor; Adalimumab; Biomarkers; Gene expression; Longitudinal studies; Rheumatoid arthritis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number NIHR National Inst Health Research BRC MRC (Medical Research Council) R116825 |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 May 2021 10:05 |
Last Modified: | 26 May 2021 10:05 |
Status: | Published |
Publisher: | BMC |
Identification Number: | 10.1186/s13075-021-02451-9 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:174633 |
Commentary/Response Threads
- Oliver, J, Nair, N, Orozco, G, Smith, S, Hyrich, KL, Morgan, A, Isaacs, J, Wilson, AG, BRAGGSS, Barton, A and Plant, D Transcriptome-wide study of TNF-inhibitor therapy in rheumatoid arthritis reveals early signature of successful treatment. (deposited 26 May 2021 10:05) [Currently Displayed]