Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: randomized comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone. COBRA Trial Group. Combinatietherapie Bij Reumatoïde Artritis

Br J Rheumatol. 1998 Oct;37(10):1102-9. doi: 10.1093/rheumatology/37.10.1102.


Objective: Assessment of the cost-effectiveness and cost-utility of early intervention in rheumatoid arthritis (RA) patients, with combined step-down prednisolone, methotrexate and sulphasalazine, compared to sulphasalazine alone.

Methods: Multicentre 56 week randomized double-blind trial with full economic analysis of direct costs and utility analysis with rating scale and standard gamble measurement techniques.

Results: The combined-treatment group included 76 patients and the sulphasalazine group 78 patients. The mean total costs per patient in the first 56 weeks of follow-up were $5519 for combined treatment and $6511 for treatment with sulphasalazine alone (P = 0.37). Out-patient care, in-patient care and non-health care each contributed about one-third to the total costs. The combined-treatment group appeared to generate savings in the length of hospital stay for RA, non-protocol drugs and costs of home help, but comparisons were not statistically significant. Protocol drugs and monitoring were slightly more expensive in the combined-treatment group. Clinical, radiographic and functional outcomes significantly favoured combined treatment at week 28 (radiography also at week 56). Utility scores also favoured combined treatment.

Conclusion: Combined treatment is cost-effective due to enhanced efficacy at lower or equal direct costs.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / economics*
  • Cost-Benefit Analysis
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Joints / pathology
  • Joints / physiopathology
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Prednisolone / administration & dosage
  • Prednisolone / therapeutic use*
  • Severity of Illness Index
  • Sulfasalazine / administration & dosage
  • Sulfasalazine / therapeutic use*
  • Treatment Outcome


  • Antirheumatic Agents
  • Sulfasalazine
  • Prednisolone
  • Methotrexate