RESEARCH - The safety of anti-TNF treatments in RA

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Ann Rheum Dis. Published Online First: 27 August 2008.

doi:10.1136/ard.2008.091025

Copyright © 2008 BMJ Publishing Group Ltd & European League Against

Rheumatism

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Extended Report

The safety of anti-Tumor Necrosis Factor treatments in rheumatoid

arthritis: meta and exposure adjusted pooled analyses of serious

adverse events

Leombruno 1*, R. Einarson 1 and C Keystone 2

1 Department of Pharmaceutical Sciences Pharmacoepidemiology, Canada

2 University of Toronto. Mount Sinai Hospital, Canada

Abstract

Objective: To evaluate the safety of biologic treatments for

rheumatoid arthritis (RA) using results from randomized controlled

trials (RCTs).

Methods: We searched the literature to December 2007 for RCTs

evaluating inhibitors of tumour necrosis factor alpha (anti-TNFs) for

RA. Safety data was abstracted and risk estimates were calculated

using three approaches, meta-analysis with and without adjustment for

exposure and simple exposure adjusted pooling.

Results: Eighteen randomized trials involving 8,808 RA subjects were

included. Treatment with recommended doses of anti-TNFs found no

increase in the odds of death (OR=1.39, 95%CI 0.74-2.62), serious

adverse events (OR=1.11; 95%CI 0.94-1.32), serious infection (OR=1.21;

95%CI 0.89-1.63), lymphoma (OR=1.26; 95%CI 0.52-3.06), non-melanoma

skin cancers (OR=1.27; 95%CI 0.67-2.42) or the composite endpoint of

non-cutaneous cancers plus melanomas (OR=1.31; 95%CI 0.69-2.48) when

evaluated using the unadjusted meta-analytic method. Risk estimates

were similar with the other methods. For subjects who received two to

three times the recommended doses of anti-TNF the risk of serious

infection was increased with the unadjusted meta-analytic and pooled

analysis; 2.07 (95%CI:1.31-3.26) and 1.83 (95%CI:1.18-2.85)

respectively but not increased in the exposure adjusted meta-analysis

1.99 (95%CI:0.90-4.37). Meta-regression identified that the risk of

serious infection with anti-TNF therapy decreases with increasing

trial duration (p=0.035).

Conclusion: Meta-analytic and exposure adjusted pooled analyses on

over 8,800 RA subjects in RCTs treated over an average of 0.8 years

did not identify an increased risk of serious adverse events with

recommended doses. High dose anti-TNF therapy was associated with a

twofold increase in the risk of serious infections.

http://ard.bmj.com/cgi/content/abstract/ard.2008.091025v1

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