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Lookup NU author(s): Dr Ken BakerORCiD, Andrew Skelton, Dr Dennis LendremORCiD, Adam Scadeng, Dr Ben Thompson, Dr Arthur PrattORCiD, Professor John IsaacsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background Many patients with rheumatoid arthritis (RA) achieve disease remission with modern treatment strategies. However, having achieved this state, there are no tests that predict when withdrawal of therapy will result in drug-free remission rather than flare. We aimed to identify predictors of drug-free remission in RA.MethodsThe Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study was a unique, prospective, interventional cohort study of complete and abrupt cessation of conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA of at least 12 months duration and in clinical and ultrasound remission discontinued DMARDs and were monitored for six months. The primary outcome was time-to-flare, defined as disease activity score in 28 joints with C-reactive protein (DAS28-CRP) ≥ 2.4. Baseline clinical and ultrasound measures, circulating inflammatory biomarkers, and peripheral CD4+ T cell gene expression were assessed for their ability to predict time-to-flare and flare/remission status by Cox regression and receiver-operating characteristic (ROC) analysis respectively.Results23/44 (52%) eligible patients experienced an arthritis flare after a median (IQR) of 48 (31.5–86.5) days following DMARD cessation. A composite score incorporating five baseline variables (three transcripts [FAM102B, ENSG00000228010, ENSG00000227070], one cytokine [interleukin-27], one clinical [Boolean remission]) differentiated future flare from drug-free remission with an area under the ROC curve of 0.96 (95% CI 0.91–1.00), sensitivity 0.91 (0.78–1.00) and specificity 0.95 (0.84–1.00).ConclusionWe provide proof-of-concept evidence for predictors of drug-free remission in RA. If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits.
Author(s): Baker KF, Skelton AJ, Lendrem DW, Scadeng A, Thompson B, Pratt AG, Isaacs JD
Publication type: Article
Publication status: Published
Journal: Journal of Autoimmunity
Year: 2019
Volume: 105
Print publication date: 01/12/2019
Online publication date: 04/07/2019
Acceptance date: 29/06/2019
Date deposited: 09/07/2019
ISSN (print): 0896-8411
ISSN (electronic): 1095-9157
Publisher: Elsevier
URL: https://doi.org/10.1016/j.jaut.2019.06.009
DOI: 10.1016/j.jaut.2019.06.009
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