Background/Purpose: Disease flares frequently occur in patients with rheumatoid arthritis (RA). It has been suggested that these may spontaneously remit, in which case targeted treatment including intensification at the time of a flare could entail overtreatment. We investigated the occurrence and outcomes of flares during long-term follow-up in early RA patients who were treated to target over 10 years. 

Methods: In the BeSt study, which enrolled 508 patients, targeted treatment aimed at a disease activity score (DAS) ≤2.4. A flare was defined from the second year of follow-up onwards as a DAS >2.4 and an increase in DAS of ≥0.6 from the previous DAS, regardless of the height of the previous DAS, measured during 3-monthly visits. Of 480 patients sufficient follow-up data were available to apply this definition. Functional ability (health assessment questionnaire, HAQ) during a flare was compared to functional ability during the absence of a flare with a linear mixed model (LMM). Visual analogue scales (VAS) (increase of ≥20mm between two visits, yes/no) and radiographic progression (Sharp van der Heijde score; increase ≥0.5 during 1 year, yes/no) were analysed similarly with a generalized LMM.

Results: The incidence of flares was 7 – 11% per visit during year 2 to 4 of follow-up, and 4 – 6% per visit during the later years of follow-up. During year 2 to year 10, 321/480 patients (67%) experienced at least one flare with a median (interquartile range) frequency of 4 (2 – 8) times. At the time of a flare, functional ability decreased with a mean difference of 0.25 in HAQ (p<0.001). During a flare, the odds ratio (95% confidence interval) for an increase of ≥20mm in VAS compared to the previous visit was 8.8 (7.3 - 9.8), 9.6 (7.2 - 9.7) and 5.6 (4.8 - 6.6) for patient’s assessment of disease activity, pain and morning stiffness, respectively, compared to the absence of a flare. The odds ratio for developing radiographic progression in a year a flare occurred was 1.7 (95% confidence interval 1.1 - 2.8), compared to a year without a flare. In patients without any flare during follow-up, median (IQR) radiographic progression from baseline to year 10 was 1.3 (0.0 – 3.1). The more flares occurred, the higher progression rates were observed: median (IQR) SHS progression was 2.3 (0.5 – 9.6), 3.0 (0.0 – 10.0) and 4.3 (0.5 – 20.1) in patients who experienced 1, 2 and ≥3 flares during follow-up, respectively (p=0.005). A similar dose response relation was shown for functioning; in patients without any flare during follow-up, median (IQR) HAQ was 0.0 (0.0 – 0.5) at year 10, and was 0.4 (0.0 – 0.9), 0.6 (0.1 – 0.9) and 0.8 (0.4 – 1.3) in patients with 0, 1, 2, or ≥3 flares during follow-up, respectively (p<0.001).

Conclusion: Disease flares in rheumatoid arthritis are associated with short term deterioration in functioning and pain as well as radiographic damage progression, and show a dose response relation with long term functional disability and joint damage. The incidence of flares was low, and with a treatment strategy targeted at DAS≤2.4, the frequency of flares further decreased over time. This suggests that the disease may become more indolent in the majority of patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/disease-flares-during-10-year-follow-up-in-patients-with-rheumatoid-arthritis-are-associated-with-joint-damage-progression-and-disability/