title: Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial.
abstract: OBJECTIVE
  To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial.
  
  
  METHODS
  400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered.
  
  
  RESULTS
  Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006).
  
  
  CONCLUSIONS
  For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile.
  2008-007225-39.
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Leuven, Belgium Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Verschueren
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Leuven, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: De Cock
authors.affiliation: Reuma-instituut Hasselt, Hasselt, Belgium Jessa Ziekenhuis Hasselt, Hasselt, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Corluy
authors.affiliation: ZNA Jan Palfijn Antwerpen, Antwerpen, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Joos
authors.affiliation: Reuma-instituut Hasselt, Hasselt, Belgium Jessa Ziekenhuis Hasselt, Hasselt, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Langenaken
authors.affiliation: Heilig Hart Ziekenhuis Leuven, Leuven, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Taelman
authors.affiliation: ZNA Jan Palfijn Antwerpen, Antwerpen, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Raeman
authors.affiliation: Department of Rheumatology, Onze-Lieve-Vrouw Ziekenhuis Aalst, Aalst, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Ravelingien
authors.affiliation: AZ Groeninge Hospital Kortrijk, Kortrijk, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Vandevyvere
authors.affiliation: Reuma-instituut Hasselt, Hasselt, Belgium Jessa Ziekenhuis Hasselt, Hasselt, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Lenaerts
authors.affiliation: ZNA Jan Palfijn Antwerpen, Antwerpen, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Geens
authors.affiliation: ReumaClinic Genk & UHasselt, Hasselt, Belgium Maastricht UMC, Maastricht, the Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Geusens
authors.affiliation: ReumaClinic Genk & UHasselt, Hasselt, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vanhoof
authors.affiliation: AZ Groeninge Hospital Kortrijk, Kortrijk, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Durnez
authors.affiliation: Reuma-instituut Genk, Genk, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Remans
authors.affiliation: Department of Rheumatology, Onze-Lieve-Vrouw Ziekenhuis Aalst, Aalst, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Vander Cruyssen
authors.affiliation: Imeldaziekenhuis Bonheiden, Bonheiden, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Van Essche
authors.affiliation: ReumaClinic Hasselt, Hasselt, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Sileghem
authors.affiliation: AZ Sint Lucas Brugge, Brugge, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: De Brabanter
authors.affiliation: Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Joly
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Meyfroidt
authors.affiliation: Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium Skeletal Biology and Engineering Research Center, KU Leuven Department of Public Health and Primary Care, Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Van der Elst
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Leuven, Belgium Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Westhovens
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D061345:Early Medical Intervention; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D018570:Risk Assessment; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D007555:Isoxazoles; D012460:Sulfasalazine; D000077339:Leflunomide; D011241:Prednisone; D008727:Methotrexate
keywords: Corticosteroids; DMARDs (synthetic); Early Rheumatoid Arthritis; Methotrexate; Outcomes research