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Ann Rheum Dis. 2010 Jan;69(1):186-92. doi: 10.1136/ard.2009.115832.

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.

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1
Department of Epidemiology and Biostatistics, VU University Medical Centre, PK 6Z 165, PO Box 7057, 1007 MB Amsterdam, The Netherlands. eb@vumc.nl

Abstract

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.

PMID:
19773287
DOI:
10.1136/ard.2009.115832
[Indexed for MEDLINE]
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