title: Chronicity of rheumatoid arthritis affects the responsiveness of physical function, but not of disease activity measures in rheumatoid arthritis clinical trials.
abstract: BACKGROUND
  In previous studies it has been indicated that functional measures are less responsive in patients with established or late rheumatoid arthritis (RA) as compared with early RA, potentially because chronic irreversible functional damage is present. Therefore, they may not be useful as disease activity measures. We aimed to investigate whether this is specific to functional measures, or if it similarly also relates to other typical RA disease activity measures.
  
  
  METHODS
  We performed a pooled analysis of patient level clinical trial data of patients with RA. We investigated the effects of duration of RA on the responsiveness of all RA core set measures by using logistic regression analysis. We performed a number of sensitivity analyses to support our findings.
  
  
  RESULTS
  The probability of response in functional scores decreased from ~60% in early disease to ~30% in established/late disease (p=0.0023). No other core set variable or composite index behaved in this way. The effect of chronicity solely on functional responses was confirmed in all sensitivity analyses, particularly also when joint damage was used as a surrogate of chronicity, responsiveness decreased from >60% in patients with little structural damage to <20% in patients with severe joint damage (p<0.001).
  
  
  CONCLUSIONS
  Physical function is among the most important outcomes of RA, but in contrast with other core set measures it is not a reliable measure for disease activity.
authors.affiliation: Division of Rheumatology, Medical University Vienna, Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aletaha
authors.affiliation: Division of Rheumatology, Medical University Vienna, Vienna, Austria.
authors.forename: Farideh
authors.initials: F
authors.lastname: Alasti
authors.affiliation: Division of Rheumatology, Medical University Vienna, Vienna, Austria Second Department of Medicine, Hietzing Hospital, Vienna, Austria.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D018450:Disease Progression; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007555:Isoxazoles; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000077339:Leflunomide; D000068800:Etanercept; D008727:Methotrexate