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Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis
  1. Lilian H D van Tuyl (l.vantuyl{at}
  1. VU University Medical Centre, Netherlands
    1. Maarten Boers (m.boers{at}
    1. VU University Medical Centre, Netherlands
      1. Willem F Lems (wf.lems{at}
      1. VU University Medical Centre, Netherlands
        1. Robert BM Landewé (r.landewe{at}
        1. University Hospital Maastricht, Netherlands
          1. Huub Han (hank{at}
          1. Medical Center Rijnmond Zuid, Netherlands
            1. Sjef van der Linden (s.vander.linden{at}
            1. University Hospital Maastricht, Netherlands
              1. Mart A F J van der Laar (m.vandelaar{at}
              1. Medisch Spectrum Twente & Universiteit Twente, Netherlands
                1. Rene Westhovens (rene.westhovens{at}
                1. University Hospital Leuven, Belgium
                  1. J Christiaan Van Denderen (c.v.denderen{at}
                  1. Jan van Breemen Instituut, Netherlands
                    1. Marie-Louise Westedt (mwestedt{at}
                    1. Bronovo Hospital, Netherlands
                      1. André J Peeters (peeters{at}
                      1. Reinier de Graaf Hospital, Netherlands
                        1. Piet Jacobs (p.jacobs{at}
                        1. Sint Laurentius Hospital, Netherlands
                          1. Tom W J Huizinga (t.w.j.huizinga{at}
                          1. Leiden University Medical Center, Netherlands
                            1. Hans van den Brink (hvandenbrink{at}
                            1. Medical Center Alkmaar, Netherlands
                              1. Ben A C Dijkmans (bac.dijkmans{at}
                              1. VU University Medical Centre, Netherlands
                                1. Alexandre E Voskuyl (ae.voskuyl{at}
                                1. VU University Medical Centre, Netherlands


                                  Background: COBRA combination therapy is effective for the treatment of rheumatoid arthritis (RA), but long term safety is unknown. This study evaluates survival, comorbidities and joint damage in the original COBRA trial cohort.

                                  Methods: In the COBRA trial, 155 early RA patients were treated with sulfasalazine monotherapy (SSZ-group) or a combination of step-down prednisolone, methotrexate and sulfasalazine (COBRA-group). The current 11-year follow-up study of the COBRA trial invited all original patients and performed protocollized scrutiny of clinical records, questionnaires, physical examination, laboratory and imaging tests.

                                  Results: 152 out of 155 patients yielded at least partial data. After mean 11 years follow-up, 18 (12%) patients had died, 6 COBRA patients and 12 SSZ patients, hazard ratio 0.57 (95%CI: 0.21-1.52). Treatment for hypertension was significantly more prevalent in the COBRA-group (P=0.02) with similar trends for diabetes and cataract. Conversely, hypercholesterolemia, cancer and infection showed a trend in favour of COBRA. Other comorbidities such as cardiovascular disease and fractures appeared in similar frequency. Radiographic findings suggest as a minimum sustained benefit for COBRA therapy, i.e. difference in joint damage but similar subsequent progression rates after 5 years. Imputation to compensate for selective dropout suggests increasing benefit for COBRA, i.e. difference in yearly progression rates similar to that seen in the first 5 years of follow-up.

                                  Conclusions: After 11 years, initial COBRA combination therapy resulted in numerically lower mortality and similar prevalence of comorbidity compared to initial SSZ monotherapy. In addition, lower progression of joint damage suggests long-term disease modification.

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