Randomized, placebo controlled trial of withdrawal of slow-acting antirheumatic drugs and of observer bias in rheumatoid arthritis

Scand J Rheumatol. 1996;25(4):194-9. doi: 10.3109/03009749609069987.


Patients with rheumatoid arthritis, in stable treatment with methotrexate, penicillamine, or sulfasalazine, were randomized in a double-blind fashion either to continuation of their usual treatment or to placebo. 112 patients were included; 52 patients who refused participation had no more severe disease than the others. The patients felt worse on placebo than on active drug (p = 0.002). The mean differences in number of tender, painful and swollen joints after one month were 2.4 (p = 0.08), 3.0 (p = 0.12) and 2.2 (p = 0.03), respectively. Treatment failure occurred for 42 patients of whom 33 received placebo (p = 0.000,001). There was no difference in the severity of side effects (p = 0.91). The patients guessed their treatment correctly more often than expected (p = 0.02) because of the perceived effect. None of the two observers guessed better than chance, and there were no differences between the observers' evaluations of the joints. The effect of slow-acting antirheumatic drugs was unequivocal and no observer bias occurred.

Publication types

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

MeSH terms

  • Aged
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology*
  • Arthritis, Rheumatoid / psychology
  • Humans
  • Middle Aged
  • Observer Variation
  • Self-Assessment
  • Severity of Illness Index
  • Substance Withdrawal Syndrome / epidemiology*
  • Substance Withdrawal Syndrome / psychology
  • Time Factors


  • Antirheumatic Agents