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.
Purpose: To study whether a 3-month placebo period is sufficient to prove efficacy.
Methods: Meta-analysis of placebo- or active control trials of biologic 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 -50 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 due to further improvement only in the experimental groups. In active control trials contrasts were smaller, and for ACR50 and-70 these decreased somewhat due 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 to then switch placebo patients to standard of care, allowing a more valid and comprehensive assessment including safety.
Statistics from Altmetric.com
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.