Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae

Abstract

BackgroundRA 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.MethodsPeople 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.ResultsDAS28 (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.ConclusionFlares 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.

Insights Into the Concept of Rheumatoid Arthritis Flare

“…Modification of disease activity in RA is strongly related to pain, a subjective domain concretized with visual analog or numerical rating scales ( 9 ). Pain perception can be associated with tender joints or exist without elicitable joint pain.…”

“…Of interest, McWilliams et al ( 9 ) recently proposed a new flare entity based primarily on pain and assessed by the SF36-bodily pain scale. They identified patients experiencing abrupt (primary) or progressive (incremental) pain flares as suggested by a minimal predetermined variation in the SF36-bodily pain scale.…”

Pain Mechanism in Rheumatoid Arthritis: From Cytokines to Central Sensitization

“…There is no doubt about the contribution of inflammation to RA pain, but research shows that there is a discrepancy between doctors' assessment of inflammation and patients' reported pain, with 64% of participants in pain flare not concurrently in DAS28 flare and 60% of those in DAS28 flare not concurrently in pain flare [ 11 ]. During acute synovitis, the intensity of pain is related to the severity of inflammation, but the association between pain and joint inflammation is often weak before disease flaring and after the suppression of inflammatory disease [ 5 , 12 – 17 ].…”

Defining and managing flares in axial spondyloarthritis

“…The second potential consequence of flares is related to structural damage [41]. It is well acknowledged today that a strong correlation exists between disease activity and structural progression [42].…”