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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
  1. Patrick Verschueren1,2,
  2. Diederik De Cock1,
  3. Luk Corluy3,4,
  4. Rik Joos5,
  5. Christine Langenaken3,4,
  6. Veerle Taelman6,
  7. Frank Raeman5,
  8. Isabelle Ravelingien7,
  9. Klaas Vandevyvere8,
  10. Jan Lenaerts3,4,
  11. Elke Geens5,
  12. Piet Geusens9,10,
  13. Johan Vanhoof9,
  14. Anne Durnez8,
  15. Jan Remans11,
  16. Bert Vander Cruyssen7,
  17. Els Van Essche12,
  18. An Sileghem13,
  19. Griet De Brabanter14,
  20. Johan Joly2,
  21. Sabrina Meyfroidt1,
  22. Kristien Van der Elst2,15,
  23. Rene Westhovens1,2
    1. 1KU Leuven Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium
    2. 2Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium
    3. 3Reuma-instituut Hasselt, Hasselt, Belgium
    4. 4Jessa Ziekenhuis Hasselt, Hasselt, Belgium
    5. 5ZNA Jan Palfijn Antwerpen, Antwerp, Belgium
    6. 6Heilig Hart Ziekenhuis Leuven, Leuven, Belgium
    7. 7Rheumatology Department, Onze-Lieve-Vrouw Ziekenhuis Aalst, Aalst, Belgium
    8. 8AZ Groeninge Hospital Kortrijk, Kortrijk, Belgium
    9. 9ReumaClinic Genk & UHasselt, Genk, Belgium
    10. 10Maastricht UMC, Maastricht, The Netherlands
    11. 11Reuma-instituut Genk, Genk, Belgium
    12. 12Imeldaziekenhuis Bonheiden, Bonheiden, Belgium
    13. 13ReumaClinic Hasselt, Hasselt, Belgium
    14. 14AZ Sint Lucas Brugge, Bruges, Belgium
    15. 15KU Leuven Department of Public Health and Primary Care, Skeletal Biology and Engineering Research Center, Leuven, Belgium
    1. Correspondence to Dr Diederik De Cock, Department of Rheumatology, UZ Herestraat 49—bus 7003, Leuven 3000, Belgium; diederik.decock{at}med.kuleuven.be

    Abstract

    Objectives 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.

    Trial registration numbers EudraCT-number 2008-007225-39 and NCT01172639; Results.

    • Early Rheumatoid Arthritis
    • Corticosteroids
    • DMARDs (synthetic)
    • Treatment
    • Methotrexate

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