Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis

Lancet. 1996 Feb 10;347(8998):347-52. doi: 10.1016/s0140-6736(96)90535-8.


Background: A favourable benefit/risk ratio for treatment of rheumatoid arthritis (RA) with second-line drugs has been established only in short-term studies. The present investigation addresses the question of whether RA patients with a good response to long-term treatment with second-line drugs benefit from continuation of such treatment.

Methods: A 52-week randomised double-blind placebo-controlled multicentre study was conducted to assess the effect of stopping second-line therapy in 285 RA patients with a good long-term therapeutic response. The patients either continued the second-line drug (n = 142) or received a placebo (n = 143). The endpoint was a flare, defined as recurrence of synovitis.

Findings: At entry into the study median duration of second-line drug therapy was 5 years (range 2-33). At 52 weeks the cumulative incidence of a flare was 38% for the placebo group and 22% for the continued therapy group (p = 0.002). The risk of a flare was 2.0 times higher for patients receiving placebo than for those continuing the second-line drug (95% CI 1.27 to 3.17). The same trend was found for each second-line drug separately, with the exception of d-penicillamine. Side-effects that necessitated dose reduction or discontinuation occurred in 2 patients in each group.

Interpretation: Second-line drugs continue to be effective in RA patients who have responded well to initial treatment.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / prevention & control
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Life Tables
  • Male
  • Middle Aged
  • Recurrence
  • Risk Factors
  • Severity of Illness Index
  • Substance Withdrawal Syndrome / epidemiology
  • Substance Withdrawal Syndrome / etiology
  • Synovitis / chemically induced
  • Synovitis / epidemiology
  • Time Factors
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents