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Tight control and intensified COBRA combination treatment in early rheumatoid arthritis: 90% remission in a pilot trial
  1. L H D van Tuyl1,
  2. W F Lems2,
  3. A E Voskuyl2,
  4. P J S M Kerstens3,
  5. P Garnero4,
  6. B A C Dijkmans2,
  7. M Boers5
  1. 1
    Department of Clinical Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  2. 2
    Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands
  3. 3
    Jan van Breemen Institute, Amsterdam, The Netherlands
  4. 4
    INSERM Unit 664 and Synarc, Lyon, France
  5. 5
    VU University Medical Center, Clinical Epidemiology & Biostatistics, Amsterdam, The Netherlands
  1. Lilian H D van Tuyl, VU University Medical Center, Department of Clinical Epidemiology & Biostatistics, PK 6Z 159, PO Box 7057, 1007 MB Amsterdam, The Netherlands; L.vantuyl{at}


Objective: To investigate the efficacy and feasibility of an intensive combination treatment in early rheumatoid arthritis (RA) combined with monitoring both disease activity and cartilage degradation.

Methods: In a pilot trial, 21 patients with active early RA (mean DAS28 5.3; mean disease duration 3 months) were treated with COBRA treatment comprising sulfasalazine, methotrexate and high-dose step-down prednisolone, intensified by adding hydroxychloroquine and continued low-dose prednisolone. In addition, based on measurements of disease activity or a marker of cartilage degradation (CTX-II), treatment adjustments were possible with methotrexate intensification after 8 or 21 weeks; and with infliximab after 21 weeks.

Results: Nineteen of 21 patients (90%) were in remission (DAS28 <2.6) after 40 weeks (8 weeks, 57%; 21 weeks, 76%). American College of Rheumatology (ACR) criteria, ACR20, 50, 70 and 90 improvements rates were 100%, 95%, 71% and 43% respectively. CTX-II excretion decreased by mean (SD) 347(292) ng/mmol creatinine, but only 50% of patients reduced their CTX-II excretion below the cut-off point. The two monitoring groups showed no significant difference in remission according to DAS score or CTX-II excretion, despite a trend towards more intensive treatment in the CTX-II group. Treatment intensification was feasible according to protocol.

Conclusions: This small pilot study suggests that intensified and tightly controlled COBRA treatment is uniquely effective in early RA.

Trial registration number: ISRCTN96372677.

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  • Funding: This study was supported by an unrestricted research grant from Schering Plough BV.

  • Competing interests: None.

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