title: What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review.
abstract: OBJECTIVE
  Initiation of DMARD-therapy in the 'window of opportunity' is thought to result in a more effective modification of the processes underlying rheumatoid arthritis (RA). We questioned whether this effect is true or hyped and performed a systematic literature review.
  
  
  METHODS
  Medical literature databases up to June 2012 were systematically reviewed for cohort studies and randomised controlled trials reporting outcome data of early RA in relation with symptom duration at treatment initiation. The quality of these studies was assessed by two independent reviewers using a criteria scoring system of 15 items. Studies were dichotomised with the median score (79%) as cut-off. Best-evidence synthesis was applied to determine the level of evidence per outcome category. A meta-analysis was performed on the studies reporting on achieving DMARD-free sustained remission (the reverse of disease persistency).
  
  
  RESULTS
  Out of 836 screened articles, 18 fulfilled the selection criteria and were not duplicates. Ten were scored as high quality. Remission (various definitions) and radiographic progression were frequently studied outcomes. There was strong evidence for an association between symptom duration and radiographic progression. A meta-analysis on datasets evaluating DMARD-free sustained remission showed that symptom duration was independently associated with such remission; HR 0.989 (95% CI 0.983 to 0.995) per week increase in symptom duration. A moderate level of evidence was observed for other remission outcomes.
  
  
  CONCLUSIONS
  Even when heterogeneity of patients is taken into account, prolonged symptom duration is associated with radiographic progression and a lower chance on DMARD-free sustained remission. These data may support the presence of a 'window of opportunity'.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, , Leiden, The Netherlands.
authors.forename: J A B
authors.initials: JA
authors.lastname: van Nies
authors.forename: A
authors.initials: A
authors.lastname: Krabben
authors.forename: J W
authors.initials: JW
authors.lastname: Schoones
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.forename: A H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D011859:Radiography
chemical_list: D018501:Antirheumatic Agents
keywords: Early Rheumatoid Arthritis; Outcomes research; Qualitative research