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01.08.2011 | Research article | Ausgabe 4/2011 Open Access

Arthritis Research & Therapy 4/2011

The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systematic review and meta-analyses

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 4/2011
Autoren:
William G Dixon, Samy Suissa, Marie Hudson
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​ar3453) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

All authors jointly conceived the study. WGD generated the search strategy and performed the initial abstract screening. WGD and MH independently reviewed the 430 full-text articles. WGD performed the data extraction and meta-analysis. All authors helped to draft the manuscript and read and approved the final manuscript.

Abstract

Introduction

Infection is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). The objective of this study was to perform a systematic review and meta-analysis of the effect of glucocorticoid (GC) therapy on the risk of infection in patients with RA.

Methods

A systematic review was conducted by using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials database to January 2010 to identify studies among populations of patients with RA that reported a comparison of infection incidence between patients treated with GC therapy and patients not exposed to GC therapy.

Results

In total, 21 randomised controlled trials (RCTs) and 42 observational studies were included. In the RCTs, GC therapy was not associated with a risk of infection (relative risk (RR), 0.97 (95% CI, 0.69, 1.36)). Small numbers of events in the RCTs meant that a clinically important increased or decreased risk could not be ruled out. The observational studies generated a RR of 1.67 (1.49, 1.87), although significant heterogeneity was present. The increased risk (and heterogeneity) persisted when analyses were stratified by varying definitions of exposure, outcome, and adjustment for confounders. A positive dose-response effect was seen.

Conclusions

Whereas observational studies suggested an increased risk of infection with GC therapy, RCTs suggested no increased risk. Inconsistent reporting of safety outcomes in the RCTs, as well as marked heterogeneity, probable residual confounding, and publication bias in the observational studies, limits the opportunity for a definitive conclusion. Clinicians should remain vigilant for infection in patients with RA treated with GC therapy.
Zusatzmaterial
Additional file 1: Search strategy for identifying RCTs and observational studies. (DOC 33 KB)
13075_2011_3204_MOESM1_ESM.DOC
Additional file 2: Observational studies reporting risk of infection outcomes by GC therapy. (DOCX 198 KB)
13075_2011_3204_MOESM2_ESM.DOCX
Additional file 3: Sensitivity analyses of RCT and observational study meta-analyses. (DOC 34 KB)
13075_2011_3204_MOESM3_ESM.DOC
Authors’ original file for figure 1
13075_2011_3204_MOESM4_ESM.pdf
Authors’ original file for figure 2
13075_2011_3204_MOESM5_ESM.pdf
Authors’ original file for figure 3
13075_2011_3204_MOESM6_ESM.pdf
Authors’ original file for figure 4
13075_2011_3204_MOESM7_ESM.pdf
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