title: Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial.
abstract: BACKGROUND
  Recently, we documented the likely non-inferiority of Combinatietherapie Bij Reumatoïde Artritis (COBRA)-light therapy (methotrexate increased to 25 mg/week with initial prednisolone 30 mg/day) compared with the original COBRA therapy (methotrexate 7.5 mg/week, sulfasalazine 2 g/day, with initial prednisolone 60 mg/day) after 26 weeks in patients with early active rheumatoid arthritis (RA).
  
  
  OBJECTIVE
  To assess the non-inferiority of COBRA-light versus COBRA after 1 year in terms of disease activity (DAS44), functional outcome (Health Assessment Questionnaire (HAQ)) and radiographic progression (Sharp/van der Heijde score (SHS)), and to assess the effect of adding etanercept.
  
  
  METHODS
  An open-label, randomised controlled, non-inferiority trial of 162 patients with active early RA, following a treat-to-target protocol incorporating the addition of etanercept if DAS44 ≥1.6 at weeks 26 or 39.
  
  
  RESULTS
  Both groups showed major improvements in DAS44 after 52 weeks: mean (SD) -2.41 (1.2) in the COBRA and -2.02 (1.0) in the COBRA-light group (p=ns). In both groups, functional ability improved and radiological progression of joints was minimal. At least one adverse event was reported in 96% of the patients in both groups. In total, 25 serious adverse events occurred: 9 vs 16 in COBRA and COBRA-light, respectively. Treatment actually instituted was often less intensive than required by the protocol: of the total population, 108 patients (67%) required etanercept (more in the COBRA-light group), but only 67 of these (62%) actually received it.
  
  
  CONCLUSIONS
  Intensive COBRA or COBRA-light therapy has major, comparably favourable effects on disease activity, functional ability and radiological outcome after 1 year in patients with early RA. Protocolised addition of etanercept was often not implemented by treating rheumatologists, and patients receiving it appeared to have limited added benefit, probably because of low disease activity levels at its initiation.
  
  
  BACKGROUND
  ISRCTN55552928.
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, Noord Holland, The Netherlands.
authors.forename: Marieke M
authors.initials: MM
authors.lastname: ter Wee
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, Noord Holland, The Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: den Uyl
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, Noord Holland, The Netherlands Department of Rheumatology, Jan van Breemen Research Institute Reade, Amsterdam, Noord Holland, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.affiliation: Department of Rheumatology, Jan van Breemen Research Institute Reade, Amsterdam, Noord Holland, The Netherlands Westfriesgasthuis, Hoorn, Noord Holland, The Netherlands.
authors.forename: Pit
authors.initials: P
authors.lastname: Kerstens
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, Noord Holland, The Netherlands Department of Rheumatology, Jan van Breemen Research Institute Reade, Amsterdam, Noord Holland, The Netherlands.
authors.forename: Mike
authors.initials: M
authors.lastname: Nurmohamed
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, Noord Holland, The Netherlands Department of Rheumatology, Jan van Breemen Research Institute Reade, Amsterdam, Noord Holland, The Netherlands.
authors.forename: Dirkjan
authors.initials: D
authors.lastname: van Schaardenburg
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, Noord Holland, The Netherlands.
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.affiliation: Department of Rheumatology, VU University Medical Center, Amsterdam, Noord Holland, The Netherlands Department of Rheumatology, Jan van Breemen Research Institute Reade, Amsterdam, Noord Holland, The Netherlands.
authors.forename: Willem F
authors.initials: WF
authors.lastname: Lems
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D061345:Early Medical Intervention; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012460:Sulfasalazine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D012460:Sulfasalazine; D011239:Prednisolone; D000068800:Etanercept; D008727:Methotrexate
keywords: Anti-TNF; DMARDs (synthetic); Early Rheumatoid Arthritis; Outcomes research; Treatment