title: Meta-analysis suggests that intensive non-biological combination therapy with step-down prednisolone (COBRA strategy) may also 'disconnect' disease activity and damage in rheumatoid arthritis.
abstract: OBJECTIVE
  Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF) antagonists changes the relationship between disease activity and progression of radiological joint damage ('disconnect'): patients who have little or no response of disease activity still show reductions in damage progression. In early RA, the COBRA strategy (combination of methotrexate and sulfasalazine with step-down prednisolone) has been shown to be equivalent to high-dose methotrexate and infliximab in suppressing damage progression (BeSt trial). We investigated whether COBRA treatment can also 'disconnect' disease activity and damage.
  
  
  METHODS
  A meta-analysis combined data from the COBRA trial (COBRA vs sulfasalazine monotherapy) with that of two arms of the BeSt trial (COBRA vs sequential monotherapy). Linear regression related 1-year progression of damage (Sharp van der Heijde score) as a dependent variable with disease activity (time-averaged Disease Activity Score in 44 joints (DAS44) or C-reactive protein (CRP)), treatment strategy (COBRA or control) and their interaction (indicator of a disconnect) as independent variables. The main outcome was the pooled interaction term.
  
  
  RESULTS
  Complete data from 60-100% of patients were available. Before pooling, disease activity was the only (strongly) significant independent factor related to damage progression. The pooled interaction term was (weakly) significant: time-averaged DAS44×treatment interaction, one-sided p=0.027; time-averaged CRP×treatment interaction, one-sided p=0.044.
  
  
  CONCLUSIONS
  Changes in the relationship between disease activity and damage progression may not be limited to anti-TNF treatment, but a property of early, rapid and deep suppression of joint inflammation, also induced by conventional strategies that include glucocorticoids.
authors.affiliation: Department of Epidemiology & Biostatistics, VU University Medical Center, 1007 MB Amsterdam, The Netherlands. eb@vumc.nl
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.forename: Lilian
authors.initials: L
authors.lastname: van Tuyl
authors.forename: Marianne
authors.initials: M
authors.lastname: van den Broek
authors.forename: Piet J
authors.initials: PJ
authors.lastname: Kostense
authors.forename: Cornelia F
authors.initials: CF
authors.lastname: Allaart
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D006801:Humans; D007596:Joints / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage; D011239:Prednisolone / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D012460:Sulfasalazine / Q000008:administration & dosage
chemical_list: D018501:Antirheumatic Agents; D012460:Sulfasalazine; D011239:Prednisolone; D008727:Methotrexate