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Tight control and intensified COBRA combination therapy in early rheumatoid arthritis: 90% remission in a pilot trial
  1. Lilian HD van Tuyl (l.vantuyl{at}
  1. VU University Medical Center, Netherlands
    1. Willem F Lems (wf.lems{at}
    1. VU University Medical Center, Netherlands
      1. Alexandre E Voskuyl (ae.voskuyl{at}
      1. VU University Medical Center, Netherlands
        1. Pit JSM Kerstens (p.kerstens{at}
        1. Jan van Breemen Institute, Netherlands
          1. Patrick Garnero (patrick.garnero{at}
          1. Synarc SAS, France
            1. Ben AC Dijkmans (bac.dijkmans{at}
            1. VU University Medical Center, Netherlands
              1. Maarten Boers (m.boers{at}
              1. VU University Medical Center, Netherlands


                Objective: To investigate the efficacy and feasibility of an intensive combination therapy in early rheumatoid arthritis (RA) combined with monitoring of 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 therapy 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%). 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.

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

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