title: Consequences of delayed therapy with second-line agents in rheumatoid arthritis: a 3 year followup on the hydroxychloroquine in early rheumatoid arthritis (HERA) study.
abstract: OBJECTIVE
  To assess the longterm effect of delaying therapy with second-line agents in patients with early rheumatoid arthritis (RA).
  
  
  METHODS
  One hundred nineteen patients who participated in a 9 month placebo controlled randomized trial of hydroxychloroquine sulfate (HCQ) were followed prospectively for an additional 3 years. Those randomized to HCQ are referred to as the early treatment group and those randomized to placebo as the delayed treatment group. Participants were assessed annually for pain [Arthritis Impact Measurement Scales (AIMS) and Stanford Health Assessment Questionnaire (HAQ)], physical disability (AIMS and HAQ), and the RA global well being scale (AIMS). Conversion of results into standard deviation (SD) units permitted defining a substantial difference as per Felson as > 0.30 SD units and a clinically indistinguishable difference as < or = 0.06 SD units.
  
  
  RESULTS
  One hundred fifteen patients (97%) participated and complete data were available on 104 (87%). Compared to the early treatment group, the delayed group remained worse for both the pain and the physical disability outcomes over the additional 3 year followup. The difference in the RA global well being score became clinically indistinguishable for the early and delayed groups only after the 2 year post-trial assessment. The between-group differences were not explained by post-trial therapy with corticosteroids, other second-line agents, or nonsteroidal antiinflammatory drugs and analgesic preparations.
  
  
  CONCLUSIONS
  These findings show that a delay in instituting therapy with second-line agents, even a 9 month delay in instituting a moderately powerful second-line agent such as HCQ, has significant effects on longterm patient outcome, and provides strong evidence in support of early therapy in RA.
authors.affiliation: Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Tsakonas
authors.forename: A A
authors.initials: AA
authors.lastname: Fitzgerald
authors.forename: M A
authors.initials: MA
authors.lastname: Fitzcharles
authors.forename: A
authors.initials: A
authors.lastname: Cividino
authors.forename: J C
authors.initials: JC
authors.lastname: Thorne
authors.forename: A
authors.initials: A
authors.lastname: M'Seffar
authors.forename: L
authors.initials: L
authors.lastname: Joseph
authors.forename: C
authors.initials: C
authors.lastname: Bombardier
authors.forename: J M
authors.initials: JM
authors.lastname: Esdaile
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018434:Sickness Impact Profile; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine