Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up

Ann Rheum Dis. 2019 May;78(5):586-589. doi: 10.1136/annrheumdis-2018-214618. Epub 2019 Feb 26.


Objectives: Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population.

Methods: The COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression.

Results: Duration of follow-up in patients alive was mean 23 (range 22-24) years. In total, 44 patients died (28%, SMR=0.80 [95% CI 0.59 to 1.06]); 20 of 75 COBRA patients (27%, SMR 0.75 [0.47 to 1.14]) and 24 of 79 SSZ patients (30%, SMR 0.85 [0.56 to 1.25]); p=0.61). In the reference sample of the general population, 55 people (36%) died. 5 factors were significantly associated with increased mortality hazard: damage progression at 28 weeks; high Health Assessment Questionnaire (HAQ) score and absence of HLA-DR 2 or 3; disease duration from start of complaints was also significant, but showed an uninterpretable pattern.

Conclusions: This prospective trial cohort study of early RA is one of the first to show similar mortality compared with the general population after 23 years of follow-up. It confirms that early, intensive treatment of RA has long-term benefits and suggests that treating to target is especially important for patients with poor prognosis.

Keywords: arthritis; corticosteroids; dmards (synthetic); early rheumatoid arthritis; epidemiology; mortality; outcomes research; randomized clinical trial; rheumatoid.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / administration & dosage*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / mortality*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Methotrexate / administration & dosage*
  • Middle Aged
  • Prednisolone / administration & dosage*
  • Prospective Studies
  • Severity of Illness Index
  • Sulfasalazine / administration & dosage*
  • Treatment Outcome


  • Antirheumatic Agents
  • Sulfasalazine
  • Prednisolone
  • Methotrexate