Article Text


Concise report
The time has come to limit the placebo period in rheumatoid arthritis trials to 3 months: a systematic comparison of 3- and 6-month response rates in trials of biological agents


Background: Most registration trials in rheumatoid arthritis (RA) include a placebo arm in the setting of an incomplete response to disease-modifying antirheumatic treatment (DMARD-IR). A minimum duration of 6 months is required despite serious methodological and ethical shortcomings.

Objective: To study whether a 3-month placebo period is sufficient to prove efficacy.

Methods: Meta-analysis of placebo- or active control trials of biological agents in DMARD-IR RA, comparing the contrast in ACR response between experimental and control groups at 3 and 6 months.

Results: Twenty trials yielded 15 placebo and 18 active control contrasts (>10 000 patients). At 3 months active treatment showed a highly significant contrast with placebo for ACR20 and ACR50 in every instance. As all groups improved further the mean contrast at 6 months was unchanged. For ACR70 the contrast was clearly greater at 6 months owing to further improvement only in the experimental groups. In active control trials contrasts were smaller, and for ACR50 and ACR70 these decreased somewhat owing to “catch-up” responses in the control groups.

Conclusion: The placebo phase of registration trials for RA can be limited to 3 months. An accompanying viewpoint proposes that patients receiving placebo should then be switched to standard of care, allowing a more valid and comprehensive assessment, including safety.

Statistics from


Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles