RESEARCH - The time has come to limit the placebo period in RA trials to 3 months

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Ann Rheum Dis. 2009 Sep 22.

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 biologic agents.

Boers M.

VUmc, Netherlands.

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.

PMID: 19773287

http://www.ncbi.nlm.nih.gov/pubmed/19773287

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