Background 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.
Objectives To study 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 2nd 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 2 visits, yes/no) and radiographic progression (Sharp vd 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 10, 321/480 patients (67%) experienced at least one flare with a median (IQR) frequency of 2 (1 - 4) 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 (CI)) for an increase of ≥20mm in VAS compared to the previous visit was 8.5 (7.3-9.8), 8.4 (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% CI 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).
Conclusions DAS-defined 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 captured incidence of flares was low, and with a continued treatment strategy targeted at DAS ≤2.4, the frequency of flares further decreased over time. This suggests that the disease becomes more indolent in the majority of patients.
Disclosure of Interest I. Markusse: None declared, L. Dirven: None declared, H. Han: None declared, M. van Oosterhout: None declared, A. Schouffoer: None declared, P. Kerstens: None declared, W. Lems: None declared, T. Huizinga: None declared, C. Allaart Grant/research support from: The study was designed by the investigators and supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. Data collection, trial management, data analysis and preparation of the manuscript were performed by the authors.