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Disease Activity Flares and Pain Flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae

McWilliams, Daniel F.; Rahman, Shimin; James, Richard; Ferguson, Eamonn; Kiely, Patrick; Young, Adam; Walsh, David


Daniel F. McWilliams

Shimin Rahman

Richard James

Eamonn Ferguson

Patrick Kiely

Adam Young

David Walsh


RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities.
People from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n=719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥0.6 points if inactive RA). A ≥4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups.
DAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode.
Flares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.

Journal Article Type Article
Publication Date Nov 18, 2019
Journal BMC Rheumatology
Electronic ISSN 2520-1026
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 3
Article Number 49
Pages 1-9
APA6 Citation McWilliams, D. F., Rahman, S., James, R., Ferguson, E., Kiely, P., Young, A., & Walsh, D. (2019). Disease Activity Flares and Pain Flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae. BMC Rheumatology, 3, 1-9.
Keywords rheumatoid arthritis, flare, inflammation, pain
Publisher URL
Additional Information Received: 21 March 2019; Accepted: 10 October 2019; First Online: 18 November 2019; : Trent Research Ethics Committee (01/4/047) approved the ERAN study. Written informed consent was obtained from all participants in line with the Declaration of Helsinki.; : Not applicable.; : All other authors declare no competing interests for the work in this study. DAW and DFM have received grant support from Pfizer for other research.


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