RESEARCH - The safety of anti-TNF treatments in RA: meta and exposure adjusted pooled analyses of serious adverse events

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Ann Rheum Dis. 2008 Aug 27.

The safety of anti-Tumor Necrosis Factor treatments in rheumatoid

arthritis: meta and exposure adjusted pooled analyses of serious

adverse events.

Leombruno JP, Einarson TR, Keystone EC.

Department of Pharmaceutical Sciences Pharmacoepidemiology, Canada.

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.

PMID: 18753157

http://www.ncbi.nlm.nih.gov/pubmed/18753157

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