title: A non-inferiority trial of an attenuated combination strategy ('COBRA-light') compared to the original COBRA strategy: clinical results after 26 weeks.
abstract: BACKGROUND
  Early, intensive treatment of rheumatoid arthritis (RA) with the combination of (initially high dose) prednisolone, methotrexate and sulfasalazine (COBRA therapy) considerably lowers disease activity and suppresses radiological progression, but is infrequently prescribed in daily practice. Attenuating the COBRA regimen might lessen concerns about side effects, but the efficacy of such strategies is unknown.
  
  
  OBJECTIVE
  To compare the 'COBRA-light' strategy with only two drugs, comprising a lower dose of prednisolone (starting at 30 mg/day, tapered to 7.5 mg/day in 9 weeks) and methotrexate (escalated to 25 mg/week in 9 weeks) to COBRA therapy (prednisolone 60 mg/day, tapered to 7.5 mg/day in 6 weeks, methotrexate 7.5 mg/week and sulfasalazine 2 g/day).
  
  
  METHODS
  An open, randomised controlled, non-inferiority trial in 164 patients with early active RA, all treated according to a treat to target strategy.
  
  
  RESULTS
  At baseline patients had moderately active disease: mean (SD) 44-joint disease activity score (DAS44) 4.13 (0.81) for COBRA and 3.95 (0.9) for COBRA-light. After 6 months, DAS44 significantly decreased in both groups (-2.50 (1.21) for COBRA and -2.18 (1.10) for COBRA-light). The adjusted difference in DAS44 improvement between the groups, 0.21 (95% CI -0.11 to 0.53), was smaller than the predefined clinically relevant difference of 0.5. Minimal disease activity (DAS44 <1.6) was reached in almost half of patients in both groups (49% and 41% in COBRA and COBRA-light, respectively).
  
  
  CONCLUSIONS
  At 6 months COBRA-light therapy is most likely non-inferior to COBRA therapy.
  
  
  BACKGROUND
  55552928.
authors.affiliation: Department of Rheumatology, VU University Medical Center, , Amsterdam, The Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: den Uyl
authors.forename: Marieke
authors.initials: M
authors.lastname: ter Wee
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.forename: Pit
authors.initials: P
authors.lastname: Kerstens
authors.forename: Alexandre
authors.initials: A
authors.lastname: Voskuyl
authors.forename: Mike
authors.initials: M
authors.lastname: Nurmohamed
authors.forename: Hennie
authors.initials: H
authors.lastname: Raterman
authors.forename: Dirkjan
authors.initials: D
authors.lastname: van Schaardenburg
authors.forename: Nancy
authors.initials: N
authors.lastname: van Dillen
authors.forename: Ben
authors.initials: B
authors.lastname: Dijkmans
authors.forename: Willem
authors.initials: W
authors.lastname: Lems
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D061345:Early Medical Intervention / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use*; D012460:Sulfasalazine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D012460:Sulfasalazine; D011239:Prednisolone; D008727:Methotrexate
keywords: Corticosteroids; DMARDs (synthetic); Early Rheumatoid Arthritis; Treatment