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Characterization of a subset of patients with rheumatoid arthritis for whom current management strategies are inadequate

Jury, E; Manson, J; Ciurtin, C; Bradford, C; McDonnell, T; Isenberg, D; Robinson, G; (2019) Characterization of a subset of patients with rheumatoid arthritis for whom current management strategies are inadequate. ACR Open Rheumatology , 1 (3) pp. 145-155. 10.1002/acr2.1021. Green open access

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Abstract

Objectives: A subset of patients with seropositive rheumatoid arthritis (RA) do not mount a C-reactive protein (CRP) response during flares. We hypothesize that these patients are more likely to experience poor clinical care and less likely to respond to traditional therapy. This study questioned whether this presentation was associated with worse disease outcome and distinct immunological features. Methods: Using Power Doppler ultrasound 48 RA patients with active synovitis were recruited; 30 had normal-(n)CRP (≤5mg/L) and 18 had high-(h)CRP (>5mg/L) levels. All had equivalent disease burden assessed by other clinical and laboratory parameters. Results: Time to diagnosis and time to first disease modifying anti-rheumatic drug were significantly longer in nCRP compared to hCRP patients (p<0.05). Significantly more nCRP patients needed escalation to biologics after two year’s follow-up (p=0.01). The inflammatory milieu was also different between the two subgroups. Synergy between inflammatory cytokines observed in hCRP patients was lost in nCRP patients and nCRP patients had significantly increased regulatory T-cell (Treg) frequencies that correlated positively with predictors of poor disease outcome. Conversely, hCRP but not nCRP patients demonstrated a significant upregulation of alternative complement pathway factors which correlated negatively with Treg frequency. Conclusions: Patients with normal CRP during flares of RA had an altered immunological profile compared to hCRP patients, experienced diagnostic delays and responded less well to conventional treatment.

Type: Article
Title: Characterization of a subset of patients with rheumatoid arthritis for whom current management strategies are inadequate
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/acr2.1021
Publisher version: https://doi.org/10.1002/acr2.1021
Language: English
Additional information: © 2019 The Authors. ACR Open Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: C‐reactive protein, complement, Power doppler, rheumatoid arthritis, ultrasound
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10072315
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