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Transcriptome-wide study of TNF-inhibitor therapy in rheumatoid arthritis reveals early signature of successful treatment

Lookup NU author(s): Professor John Isaacs

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021, The Author(s).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.


Publication metadata

Author(s): OIiver J, Nair N, Orozco G, Smith S, Hyrich KL, Morgan A, Isaacs J, Wilson AG, Barton A, Plant D

Publication type: Article

Publication status: Published

Journal: Arthritis Research and Therapy

Year: 2021

Volume: 23

Issue: 1

Online publication date: 10/03/2021

Acceptance date: 11/02/2021

Date deposited: 26/03/2021

ISSN (print): 1478-6354

ISSN (electronic): 1478-6362

Publisher: BioMed Central Ltd

URL: https://doi.org/10.1186/s13075-021-02451-9

DOI: 10.1186/s13075-021-02451-9


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