Assessment of a dried blood spot C-reactive protein method to identify disease flares in rheumatoid arthritis patients

Leon D'Cruz, Kevin McEleney, Chris Cochrane, Boon Chin Tan, Priyank Shukla, Philip Gardiner, Dawn Small, Shu-Dong Zhang, David Gibson

Research output: Contribution to journalArticlepeer-review

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Abstract

Rheumatoid arthritis (RA) is characterised by painful, stiff and swollen joints. RA features sporadic ‘flares’ or inflammatory episodes—mostly occurring outside clinics—where symptoms worsen and plasma C-reactive protein (CRP) becomes elevated. Poor control of inflammation results in higher rates of irreversible joint damage, increased disability, and poorer quality of life. Flares need to be accurately identified and managed. A method comparison study was designed to assess agreement between CRP values obtained by dried blood spot (DBS) versus conventional venepuncture sampling. The ability of a weekly DBS sampling and CRP test regime to detect flare outside the clinic was also assessed. Matched venepuncture and finger lancet DBS samples were collected from n = 100 RA patients with active disease at baseline and 6 weeks (NCT02809547). A subset of n = 30 RA patients submitted weekly DBS samples over the study period. Patient demographics, including self-reported flares were recorded. DBS sample CRP measurements were made by enzyme-linked immunosorbent assay, and venepuncture samples by a reference immunoturbometric assay. Data was compared between sample types by Bland–Altman and weighted Deming regression analyses. Flare detection sensitivity and specificity were compared between ‘minimal’ baseline and 6 week sample CRP data and the ‘continuous’ weekly CRP data. Baseline DBS ELISA assay CRP measures yielded a mean positive bias of 2.693 ± 8.640 (95% limits of agreement − 14.24 to 19.63%), when compared to reference assay data. Deming regression revealed good agreement between the DBS ELISA method and reference assay data, with baseline data slope of 0.978 and intercept -0.153. The specificity of ‘continuous’ area under the curve (AUC) CRP data (72.7%) to identify flares, was greater than ‘minimal’ AUC CRP data (54.5%). This study indicates reasonable agreement between DBS and the reference method, especially at low to mid-range CRP values. Importantly, longitudinal CRP measurement in RA patients helps to clearly identify flare and thus could assist in remote monitoring strategies and may facilitate timely therapeutic intervention.
Trial registration: The Remote Arthritis Disease Activity MonitoR (RADAR) study was registered on 22/06/2016 at ClinicalTrials.gov Identifier: NCT02809547. https://clinicaltrials.gov/ct2/show/NCT02809547.
Original languageEnglish
Article number21089
Pages (from-to)21089
JournalScientific Reports
Volume10
Issue number1
Early online date3 Dec 2020
DOIs
Publication statusE-pub ahead of print - 3 Dec 2020

Bibliographical note

Funding Information:
DSG wishes to acknowledge funding from the Research and Development Office, Health and Social Care NI, The Northern Ireland Rheumatism Trust and Invest Northern Ireland in support of this work.

Publisher Copyright:
© 2020, The Author(s).

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • C-reactive protein
  • Dried Blood Spots
  • Rheumatoid Arthritis
  • Remote Monitoring
  • Flare detection

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