REVIEW - Biologics for RA: an overview of Cochrane reviews

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Sao o Med J. 2010;128(5):309-10.

Biologics for rheumatoid arthritis: an overview of Cochrane reviews.

Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R,

-Olivo MA, Ghogomu ET, Tugwell P.

Centro Cochrane do Brasil, São o, Brasil.

Abstract

BACKGROUND: the biologic disease-modifying anti-rheumatic drugs

(DMARDs) are very effective in treating rheumatoid arthritis (RA),

however there is a lack of head-to-head comparison studies.

OBJECTIVES: to compare the efficacy and safety of abatacept,

adalimumab, anakinra, etanercept, infliximab, and rituximab in

patients with RA.

METHODS: this 'Overview of Reviews' was done by including all Cochrane

Reviews on Biologics for RA available in The Cochrane Library. We

included only data on standard dosing regimens for these biologic

DMARDs from placebo-controlled trials. The primary efficacy and safety

outcomes were ACR50 and withdrawals due to adverse events. We

calculated Risk Ratios (RR) for efficacy, Odds Ratio (OR) for safety

and combined estimates of events across the placebo groups as the

expected Control Event Rate (CER). Indirect comparisons of biologics

were performed for efficacy and safety using a hierarchical linear

mixed model incorporating the most important study level

characteristic (i.e. type of biologic) as a fixed factor and study as

a random factor; reducing the between study heterogeneity by adjusting

for the interaction between the proportion of patients responding on

placebo and the duration of the trial.

MAIN RESULTS: from the six available Cochrane reviews, we obtained

data from seven studies on abatacept, eight on adalimumab, five on

anakinra, four on etanercept, four on infliximab, and three on

rituximab. The indirect comparison estimates showed similar efficacy

for the primary efficacy outcome for all biologics with three

exceptions. Anakinra was less efficacious than etanercept with a ratio

of RRs (95% CI; P value) of 0.44 (0.23 to 0.85; P = 0.014); anakinra

was less efficacious than rituximab, 0.45 (0.22 to 0.90; P = 0.023);

and likewise adalimumab was more efficacious than anakinra, 2.34 (1.32

to 4.13; P = 0.003). In terms of safety, adalimumab was more likely to

lead to withdrawals compared to etanercept, with a ratio of ORs of

1.89 (1.18 to 3.04; P = 0.009); anakinra more likely than etanercept,

2.05 (1.27 to 3.29; P = 0.003); and likewise etanercept less likely

than infliximab, 0.37 (0.19 to 0.70; P = 0.002).

AUTHORS' CONCLUSIONS: based upon indirect comparisons, anakinra seemed

less efficacious than etanercept, adalimumab and rituximab and

etanercept seemed to cause fewer withdrawals due to adverse events

than adalimumab, anakinra and infliximab. Significant heterogeneity in

characteristics of trial populations imply that these finding must be

interpreted.

PMID: 21181074

http://www.ncbi.nlm.nih.gov/pubmed/21181074

http://www.scielo.br/pdf/spmj/v128n5/a13v1285.pdf

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