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Two-year cost-effectiveness of different COBRA-like intensive remission induction schemes in early rheumatoid arthritis: a piggyback study on the pragmatic randomised controlled CareRA trial
  1. Sofia Pazmino1,
  2. Annelies Boonen2,3,
  3. Veerle Stouten1,
  4. Diederik De Cock1,
  5. Johan Joly4,
  6. Kristien Van der Elst4,
  7. Rene Westhovens1,4,
  8. Patrick Verschueren1,4
  1. 1 Department of Development and Regeneration, Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Flanders, Belgium
  2. 2 Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre, Maastricht, The Netherlands
  3. 3 Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
  4. 4 Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium
  1. Correspondence to Dr Sofia Pazmino, Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven B-3000, Belgium; sofia.pazmino{at}


Objectives To evaluate the cost-effectiveness of treat-to-target strategies among recently diagnosed patients with rheumatoid arthritis (RA) using methotrexate (MTX) and a step-down glucocorticoid (GC) scheme (COBRA Slim) compared with (1) this combination with either sulphasalazine (COBRA Classic) or leflunomide (COBRA Avant-Garde) in high-risk patients and (2) MTX without GCs (Tight-Step-Up, TSU) in low-risk patients.

Methods The incremental cost-utility was calculated from a healthcare perspective in the intention-to-treat population (n=379) of the 2-year open-label pragmatic randomised controlled Care in early RA trial. Healthcare costs were collected prospectively through electronic trial records. Quality-adjusted life years (QALYs) were estimated using mapping algorithms for EuroQoL-5 Dimension. Multiple imputation was used to handle missing data and bootstrapping to calculate CIs. Robustness was tested with biological disease-modifying antirheumatic drugs at biosimilar prices.

Results In the high-risk group, Classic (∆k€1.464, 95% CI −0.198 to 3.127) and Avant-Garde (∆k€0.636, 95% CI −0.987 to 2.258) were more expensive compared with Slim and QALYs were slightly worse for Classic (∆−0.002, 95% CI −0.086 to 0.082) and Avant-Garde (∆−0.009, 95% CI −0.102 to 0.084). This resulted in the domination of Classic and Avant-Garde by Slim. In the low-risk group, Slim was cheaper (∆k€−0.617, 95% CI −2.799 to 1.566) and QALYs were higher (∆0.141, 95% CI 0.008 to 0.274) compared with TSU, indicating Slim dominated. Results were robust against the price of biosimilars.

Conclusions The combination of MTX with a GC bridging scheme is less expensive with comparable health utility than more intensive step-down combination strategies or a conventional step-up approach 2 years after initial treatment.

Trial registration number NCT01172639.

  • early rheumatoid arthritis
  • DMARDs
  • glucocorticoids
  • cost-effectiveness
  • QALY

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  • Handling editor Josef S Smolen

  • Twitter @sophie_33pl

  • Contributors PV, RW, AB, SP and DDC made substantial contributions to the conception or design of the study. SP performed the statistical analysis. The manuscript was written by SP, PV, RW AB and DDC and subsequently revised critically by all the remaining coauthors. All authors were involved in data interpretation and approved the final version to be submitted for publication.

  • Funding The CareRA trial (EudraCT number: 2008-007225-39) was funded by a Flemish governmental grant (Agency for Innovation by Science and Technology (IWT)). Patrick Verschueren holds the Pfizer chair for early rheumatoid arthritis management at the KU Leuven.

  • Competing interests None declared.

  • Patient and public involvement statement The pragmatic CareRA protocol was strongly inspired by daily interactions of the investigators with RA patients in daily clinical practice. Patients were not formally involved in setting the research question or the outcome measures, nor were they invited to comment on study design or the interpretation of results of this manuscript. However, results of this research will be disseminated to study participants, all stakeholders and the general public in collaboration with patient organisations and the Belgian patient partners programme (trained patients who educate physicians, medicine students and other healthcare professionals in collaboration with a rheumatologist).

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the leading Ethics Committee of the University Hospitals Leuven after consulting the medical ethics committee of each participating centre (ref s51411).

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

  • Data availability statement Data are available on reasonable request. The authors commit to making the relevant anonymised patient data available for a specified purpose approved by the institution and the principal investigator of the CareRA study and with a signed data access agreement.