THU0100 Disease Activity Flares in Early Rheumatoid Arthritis Patients are Associated with Joint Damage Progression and Disability – Analysis of 10 Year Follow-up in the Best Study
Authors: I. Markusse, L. Dirven, H. Han, M. van Oosterhout, A. Schouffoer, P. Kerstens, W. Lems, T. Huizinga, C. Allaart
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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 &gt;2.4 <i>and</i> 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. <h3>Results</h3> 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&lt;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 patient9s 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&lt;0.001). <h3>Conclusions</h3> 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. <h3>Disclosure of Interest</h3> 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.