title: Disease flares in rheumatoid arthritis are associated with joint damage progression and disability: 10-year results from the BeSt study.
abstract: BACKGROUND
  Flares in patients with rheumatoid arthritis are suggested to sometimes spontaneously resolve. Targeted therapy could then entail possible overtreatment. We aimed to determine the flare prevalence in patients who are treated-to-target and to evaluate associations between flares and patient-reported outcomes and radiographic progression.
  
  
  METHODS
  In the BeSt study, 508 patients were treated-to-target for 10 years. After initial treatment adjustments to achieve disease activity score ≤2.4, a flare was defined from the second year of follow-up onwards, according to three definitions. The first definition is a disease activity score >2.4 with an increase of ≥0.6 regardless of the previous disease activity score. The other definitions will be described in the manuscript.
  
  
  RESULTS
  The flare prevalence was 4-11 % per visit; 67 % of the patients experienced ≥1 flare during 9 years of treatment (median 0 per patient per year). During a flare, functional ability decreased with a mean difference of 0.25 in health assessment questionnaire (p < 0.001), and the odds ratios (95 % confidence intervals) for an increase in patients' assessment of disease activity, pain and morning stiffness of ≥20 mm on a visual analogue scale were 8.5 (7.3-9.8), 8.4 (7.2-9.7) and 5.6 (4.8-6.6), respectively, compared to the absence of a flare. The odds ratio for radiographic progression was 1.7 (1.1-2.8) in a year with a flare compared to a year without a flare. The more flares a patient experienced, the higher the health assessment questionnaire at year 10 (p < 0.001) and the more radiographic progression from baseline to year 10 (p = 0.005).
  
  
  CONCLUSIONS
  Flares were associated with concurrent increase in patient's assessment of disease activity, pain and morning stiffness, functional deterioration and development of radiographic progression with a dose-response-effect, both during the flare and long term. This suggests that intensifying treatment during a flare outweighs the risk of possible overtreatment.
  
  
  BACKGROUND
  Dutch trial registry NTR262 (7 September 2005) and NTR265 (8 September 2005).
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. i.m.markusse@lumc.nl.
authors: Iris M
authors: IM
authors: Markusse
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. l.dirven@vumc.nl.
authors: Linda
authors: L
authors: Dirven
authors: Department of Rheumatology, Vlietland Hospital, Schiedam, The Netherlands. agerards@vlietlandziekenhuis.nl.
authors: Andreas H
authors: AH
authors: Gerards
authors: Department of Rheumatology, Fransiscus Hospital, Roosendaal, The Netherlands. whisperwoods@cs.com.
authors: Johannes H L M
authors: JH
authors: van Groenendael
authors: Department of Rheumatology, Haga Hospital, the Hague, The Netherlands. k.ronday@hagaziekenhuis.nl.
authors: H Karel
authors: HK
authors: Ronday
authors: Department of Rheumatology, Reade, Amsterdam, The Netherlands. p.kerstens@westfriesgasthuis.nl.
authors: Pit J S M
authors: PJ
authors: Kerstens
authors: Department of Rheumatology, Reade, Amsterdam, The Netherlands. wf.lems@vumc.nl.|Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. wf.lems@vumc.nl.
authors: Willem F
authors: WF
authors: Lems
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. t.w.j.huizinga@lumc.nl.
authors: Tom W J
authors: TW
authors: Huizinga
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. c.f.allaart@lumc.nl.
authors: Cornelia F
authors: CF
authors: Allaart
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004185:Disability Evaluation; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use*; D009426:Netherlands; D010146:Pain / Q000175:diagnosis; D010147:Pain Measurement; D012008:Recurrence; D012042:Registries / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate