title: Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial.
abstract: OBJECTIVE
  Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year.
  
  
  METHODS
  The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD-inexperienced patients with ERA were stratified into a high-risk or low-risk group based upon presence of erosions, disease activity, rheumatoid factor and anticitrullinated protein antibodies. High-risk patients were randomised to a COBRA Classic (MTX + sulfasalazine + prednisone step-down from 60 mg), COBRA Slim (MTX + prednisone step-down from 30 mg) or COBRA Avant Garde (MTX + leflunomide + prednisone step-down from 30 mg) scheme. Low-risk patients were randomised to MTX tight step-up (MTX-TSU) or COBRA Slim. Primary outcome was the proportion of patients in 28 joint disease activity score calculated with C-reactive protein remission at week 52 in an intention-to-treat analysis. Secondary outcomes were safety and effectiveness (ClinicalTrial.gov identifier NCT01172639).
  
  
  RESULTS
  98 COBRA Classic, 98 COBRA Slim (high risk), 93 COBRA Avant Garde, 47 MTX-TSU and 43 COBRA Slim (low risk) patients were evaluated. Remission was achieved in 64.3% (63/98) COBRA Classic, 60.2% (59/98) COBRA Slim (high risk) and 62.4% (58/93) COBRA Avant Garde patients at W52 (p=0.840); and in 57.4% (27/47) MTX-TSU and 67.4% (29/43) COBRA Slim (low risk) patients (p=0.329). Less adverse events occurred per patient with COBRA Slim (high risk) compared with COBRA Classic or COBRA Avant Garde (p=0.038). Adverse events were similar in MTX-TSU and COBRA Slim (low risk) patients (p=0.871). At W52, 76.0% patients were on DMARD monotherapy, 5.2% used GCs and 7.5% biologicals.
  
  
  CONCLUSIONS
  MTX with a moderate-dose GC remission induction scheme (COBRA Slim) seems an effective, safe, low-cost and feasible initial treatment strategy for patients with ERA regardless of their prognostic profile, provided a treat-to-target approach is followed.
  
  
  BACKGROUND
  EudraCT-number 2008-007225-39 and NCT01172639; Results.
authors.affiliation: KU Leuven Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium.|Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Verschueren
authors.affiliation: KU Leuven Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium.
authors.forename: Diederik
authors.initials: D
authors.lastname: De Cock
authors.affiliation: Reuma-instituut Hasselt, Hasselt, Belgium.|Jessa Ziekenhuis Hasselt, Hasselt, Belgium.
authors.forename: Luk
authors.initials: L
authors.lastname: Corluy
authors.affiliation: ZNA Jan Palfijn Antwerpen, Antwerp, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Joos
authors.affiliation: Reuma-instituut Hasselt, Hasselt, Belgium.|Jessa Ziekenhuis Hasselt, Hasselt, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Langenaken
authors.affiliation: Heilig Hart Ziekenhuis Leuven, Leuven, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Taelman
authors.affiliation: ZNA Jan Palfijn Antwerpen, Antwerp, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Raeman
authors.affiliation: Rheumatology Department, Onze-Lieve-Vrouw Ziekenhuis Aalst, Aalst, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ravelingien
authors.affiliation: AZ Groeninge Hospital Kortrijk, Kortrijk, Belgium.
authors.forename: Klaas
authors.initials: K
authors.lastname: Vandevyvere
authors.affiliation: Reuma-instituut Hasselt, Hasselt, Belgium.|Jessa Ziekenhuis Hasselt, Hasselt, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Lenaerts
authors.affiliation: ZNA Jan Palfijn Antwerpen, Antwerp, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Geens
authors.affiliation: ReumaClinic Genk & UHasselt, Genk, Belgium.|Maastricht UMC, Maastricht, The Netherlands.
authors.forename: Piet
authors.initials: P
authors.lastname: Geusens
authors.affiliation: ReumaClinic Genk & UHasselt, Genk, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vanhoof
authors.affiliation: AZ Groeninge Hospital Kortrijk, Kortrijk, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Durnez
authors.affiliation: Reuma-instituut Genk, Genk, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Remans
authors.affiliation: Rheumatology Department, Onze-Lieve-Vrouw Ziekenhuis Aalst, Aalst, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Vander Cruyssen
authors.affiliation: Imeldaziekenhuis Bonheiden, Bonheiden, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Van Essche
authors.affiliation: ReumaClinic Hasselt, Hasselt, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Sileghem
authors.affiliation: AZ Sint Lucas Brugge, Bruges, Belgium.
authors.forename: Griet
authors.initials: G
authors.lastname: De Brabanter
authors.affiliation: Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Joly
authors.affiliation: KU Leuven Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Meyfroidt
authors.affiliation: Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.|KU Leuven Department of Public Health and Primary Care, Skeletal Biology and Engineering Research Center, Leuven, Belgium.
authors.forename: Kristien
authors.initials: K
authors.lastname: Van der Elst
authors.affiliation: KU Leuven Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium.|Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Rene
authors.initials: R
authors.lastname: Westhovens
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000378:metabolism; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000627:therapeutic use
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D007555:Isoxazoles; D012460:Sulfasalazine; D002097:C-Reactive Protein; D000077339:Leflunomide; D011241:Prednisone; D008727:Methotrexate
keywords: Corticosteroids; DMARDs (synthetic); Early Rheumatoid Arthritis; Methotrexate; Treatment