Daily practice effectiveness of a step-down treatment in comparison with a tight step-up for early rheumatoid arthritis

Rheumatology (Oxford). 2008 Jan;47(1):59-64. doi: 10.1093/rheumatology/kem288. Epub 2007 Nov 26.


Objective: To study prospectively the daily practice effectiveness of a step-down early rheumatoid arthritis (RA) treatment strategy.

Methods: Patients with severe RA and no contra-indications were proposed step-down therapy, the others step-up. Step-down patients received a modified combination therapy in early RA (COBRA) regimen: sulphasalazine (SPS), 2 g daily, and methotrexate (MTX), 15 mg weekly, combined with step-down oral prednisolone (start 60 mg daily, fast tapering to 7.5 mg over 6 weeks, discontinuation from week 28). At week 40, patients were randomized to maintenance therapy with either SPS or MTX if disease activity score-28 (DAS28) was acceptably low. The step-up group started disease-modifying anti-rheumatic drug (DMARD) monotherapy. In both groups, treatment was adjusted at follow-up, based on DAS28. DAS28, functionality Health Assessment Questionnaire (HAQ), adverse events, DMARD changes and steroid use were registered 4-monthly for 2 yrs.

Results: Nineteen patients received step-down and 52 step-up treatment. More patients completed the first year without unplanned DMARD changes and without dosage adjustment and fewer had DMARD changes due to side effects or inefficacy in the step-down group compared with step-up, whereas the number of adverse events was comparable. MTX proved to be the most effective maintenance therapy after step-down. The DAS response, proportion of patients in remission, HAQ response and proportion of patients without disability at 4 months was higher in the step-down group.

Conclusions: In daily practice, a step-down treatment strategy for early RA is more effective than a step-up approach.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / physiopathology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Health Status
  • Humans
  • Infant
  • Joints / pathology
  • Joints / physiopathology
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Prednisolone / administration & dosage
  • Prospective Studies
  • Rheumatology / methods*
  • Severity of Illness Index
  • Sulfasalazine / administration & dosage
  • Treatment Outcome


  • Antirheumatic Agents
  • Sulfasalazine
  • Prednisolone
  • Methotrexate