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Extended report
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
  1. P Verschueren1,2,
  2. D De Cock1,
  3. L Corluy3,4,
  4. R Joos5,
  5. C Langenaken3,4,
  6. V Taelman6,
  7. F Raeman5,
  8. I Ravelingien7,
  9. K Vandevyvere8,
  10. J Lenaerts3,4,
  11. E Geens5,
  12. P Geusens9,10,
  13. J Vanhoof9,
  14. A Durnez8,
  15. J Remans11,
  16. B Vander Cruyssen7,
  17. E Van Essche12,
  18. A Sileghem13,
  19. G De Brabanter14,
  20. J Joly2,
  21. S Meyfroidt1,
  22. K Van der Elst2,15,
  23. R Westhovens1,2
  1. 1Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, 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, Antwerpen, Belgium
  6. 6Heilig Hart Ziekenhuis Leuven, Leuven, Belgium
  7. 7Department of Rheumatology, Onze-Lieve-Vrouw Ziekenhuis Aalst, Aalst, Belgium
  8. 8AZ Groeninge Hospital Kortrijk, Kortrijk, Belgium
  9. 9ReumaClinic Genk & UHasselt, Hasselt, 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, Brugge, Belgium
  15. 15Skeletal Biology and Engineering Research Center, KU Leuven Department of Public Health and Primary Care, Leuven, Belgium
  1. Correspondence to D De Cock, Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Herestraat 49, Leuven 3000, Belgium; diederik.decock{at}


Objectives 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.

EudraCT number: 2008-007225-39.

  • Early Rheumatoid Arthritis
  • DMARDs (synthetic)
  • Corticosteroids
  • Methotrexate
  • Outcomes research

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