title: Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial.
abstract: BACKGROUND
  Considering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial.
  
  
  METHODS
  Disease-modifying antirheumatic drug-naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti-citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3.2). Patients were randomized to 15 mg of MTX weekly (MTX with tight step-up (MTX-TSU)) or 15 mg of MTX weekly with prednisone bridging, starting at 30 mg and tapered to 5 mg daily from week 6 (COmbinatie therapie bij Reumatoïde Artritis (COBRA Slim)). A TSU approach was applied. Outcomes assessed were DAS28(CRP)-determined remission, cumulative disease activity, Health Assessment Questionnaire (HAQ) scores and adverse events (AEs) after 16 treatment weeks.
  
  
  RESULTS
  We analyzed 43 COBRA Slim and 47 MTX-TSU patients and found that 65.1% in the COBRA Slim group and 46.8% in the MTX-TSU group reached remission (P = 0.081). Mean ± standard deviation area under the curve values of DAS28(CRP) were 13.84 ± 4.58 and 11.18 ± 4.25 for the MTX-TSU and COBRA Slim patients, respectively (P = 0.006). More COBRA Slim patients had an HAQ score of 0 (51.2% versus 23.4%, P = 0.006) at week 16. Therapy-related AEs between groups did not differ.
  
  
  CONCLUSIONS
  In patients with low-risk eRA, MTX with step-down glucocorticoid bridging seems more efficacious than MTX step-up monotherapy, with a comparable number of AEs observed over the first 16 treatment weeks.
  
  
  BACKGROUND
  EU Clinical Trials Register Identifier: EudraCT number 2008-007225-39 . Registered 5 November 2008.
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Herestraat 49, 3000, Leuven, Belgium. patrick.verschueren@uzleuven.be.|Department of Rheumatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. patrick.verschueren@uzleuven.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: Verschueren
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Herestraat 49, 3000, Leuven, Belgium. diederik.decock@med.kuleuven.be.
authors.forename: Diederik
authors.initials: D
authors.lastname: De Cock
authors.affiliation: Reuma-Instituut Hasselt, Anne Frankplein 17, 3500, Hasselt, Belgium. luk.corluy@skynet.be.|Jessa Ziekenhuis Hasselt, Stadsomvaart 11, 3500, Hasselt, Belgium. luk.corluy@skynet.be.
authors.forename: Luk
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authors.lastname: Corluy
authors.affiliation: ZNA Jan Palfijn Antwerpen, Lange Bremstraat 70, 2170, Merksem, Belgium. rik.joos@zna.be.
authors.forename: Rik
authors.initials: R
authors.lastname: Joos
authors.affiliation: Reuma-Instituut Hasselt, Anne Frankplein 17, 3500, Hasselt, Belgium. c.langenaken@skynet.be.|Jessa Ziekenhuis Hasselt, Stadsomvaart 11, 3500, Hasselt, Belgium. c.langenaken@skynet.be.
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authors.lastname: Langenaken
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authors.forename: Frank
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authors.lastname: Raeman
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authors.forename: Isabelle
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authors.affiliation: ReumaClinic Genk & UHasselt, Jaarbeurslaan 21, 3600, Genk, Belgium. piet.geusens@scarlet.be.|Maastricht UMC, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands. piet.geusens@scarlet.be.
authors.forename: Piet
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authors.forename: Johan
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authors.forename: Anne
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authors.forename: Els
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authors.affiliation: Department of Rheumatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. kristien.vanderelst@uzleuven.be.|Skeletal Biology and Engineering Research Center, KU Leuven Department of Public Health and Primary Care, Herestraat 49, 3000, Leuven, Belgium. kristien.vanderelst@uzleuven.be.
authors.forename: Kristien
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authors.lastname: Van der Elst
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Herestraat 49, 3000, Leuven, Belgium. sabrina.meyfroidt@med.kuleuven.be.
authors.forename: Sabrina
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authors.lastname: Meyfroidt
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Herestraat 49, 3000, Leuven, Belgium. rene.westhovens@uzleuven.be.|Department of Rheumatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. rene.westhovens@uzleuven.be.
authors.forename: Rene
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mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D005938:Glucocorticoids; D002097:C-Reactive Protein; D008727:Methotrexate