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Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up
  1. Pomme BM Poppelaars1,
  2. Lilian H D van Tuyl1,
  3. Maarten Boers1,2
  1. 1 Amsterdam Rheumatology and immunology Centre, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands
  2. 2 Epidemiology & Biostatistics, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, Netherlands
  1. Correspondence to Professor Maarten Boers, Epidemiology & Biostatistics, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam 1007 MB, Netherlands; eb{at}


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.

  • early rheumatoid arthritis
  • epidemiology
  • corticosteroids
  • dmards (synthetic)
  • outcomes research
  • arthritis
  • rheumatoid
  • epidemiology
  • mortality
  • randomized clinical trial

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  • Handling editor Josef S Smolen

  • Presented at This paper was presented in plenary session at EULAR 2018.

  • Contributors All authors contributed to design, collection of data, analysis and reporting.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data is available for sharing upon request.