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Original article
Cost-utility of COBRA-light versus COBRA therapy in patients with early rheumatoid arthritis: the COBRA-light trial
  1. Marieke M ter Wee1,2,
  2. Veerle MH Coupé2,
  3. Debby den Uyl1,
  4. Birgit S Blomjous1,
  5. Esmee Kooijmans1,
  6. Pit JSM Kerstens3,
  7. Mike T Nurmohamed1,4,
  8. Dirkjan van Schaardenburg4,5,
  9. Alexandre E Voskuyl1,
  10. Maarten Boers1,2 and
  11. Willem F Lems1,4
  1. 1 Amsterdam Rheumatology and Immunology Centre, VU University Medical Center, Amsterdam, The Netherlands
  2. 2 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  3. 3 Westfriesgasthuis, Hoorn, The Netherlands
  4. 4 Amsterdam Rheumatology and Immunology Centre, Reade, Amsterdam, The Netherlands
  5. 5 Amsterdam Rheumatology and Immunology Centre, Academic Medical Centre, Amsterdam, The Netherlands
  1. Correspondence to Dr Marieke M ter Wee; m.terwee{at}


Objective To evaluate if COmbinatie therapie Bij Reumatoïde Artritis (COBRA)-light therapy is cost-effective in treating patients with early rheumatoid arthritis (RA) compared with COBRA therapy.

Methods This economic evaluation was performed next to the open-label, randomised non-inferiority COBRA-light trial in 164 patients with early RA. Non-responders to COBRA or COBRA-light received etanercept (50 mg/week) for 3–6 months. The societal perspective analysis took medical direct, non-medical direct and indirect costs into account. Costs were measured with patient cost diaries for the follow-up period of 52 weeks. Bootstrapping techniques estimated uncertainty around the cost-effectiveness ratios, presented in cost-effectiveness planes.

Results 164 patients were randomised to either COBRA or COBRA-light strategy. At week 52, COBRA-light proved to be non-inferior to COBRA therapy on all clinical outcome measures. The results of the base-case cost-utility analysis (intention-to-treat analyses) revealed that COBRA-light strategy is more expensive (k€9.3 (SD 0.9) compared with COBRA (k€7.2 (SD 0.8)), but the difference in costs were not significant (k€2.0; 95% CI –0.3 to 4.4). Also, both strategies produced similar quality-adjusted life-years (QALYs). The sensitivity analyses showed robustness of these results. In a per-protocol sensitivity analysis, in which costs of etanercept were assumed to be provided as prescribed according to protocol, both arms had much higher costs: COBRA-light: k€11.5 (8.3) compared with k€8.5 (6.8) for COBRA, and the difference in costs was significant (k€2.9; 0.6 to 5.3).

Conclusions In the base-case cost-utility analysis, the two strategies produced similar QALYs for similar costs. But it is anticipated that if protocol had been followed correctly, the COBRA-light strategy would have been more costly due to additional etanercept costs, for a limited health gain. Given the limited added benefit and high costs of starting etanercept in the presence of low disease activity in our trial, such a strategy needs better justification than is available now.

Trial registration number 55552928, Results.

  • early rheumatoid arthritis
  • cost-utility
  • economic evaluation
  • etanercept
  • prednisolone

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  • Contributors All authors have substantially contributed to the conception or design of the work; the acquisition, analysis and interpretation of data for the work. The authors revised the article critically and approved the final version to be published. All agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding This research was performed within the framework of project T1–106 of the Dutch Top Institute group, and additionally funded by an unrestricted grant from Pfizer.

  • Competing interests WFL has received speaker’s fee from Merck, AbbVie, Roche and Pfizer. MSN has received research grants from AbbVie, BMS, MSD, Pfizer, UCB and Roche. He has also acted as a consultant for AbbVie, BMS, Pfizer and Roche. Furthermore, he has participated in speakers bureau for AbbVie, BMS, Pfizer and Roche. All other authors have nothing to declare.

  • Patient consent Obtained.

  • Ethics approval Medical Ethics Committees at each participating centre approved the protocol; patients gave written informed consent before inclusion, and the study was conducted in accordance with the Declaration of Helsinki/Good Clinical Practice.

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