Rheumatoid arthritis
The Risk of Infections with Biologic Therapies for Rheumatoid Arthritis

https://doi.org/10.1016/j.semarthrit.2008.10.002Get rights and content

Objectives

To assess the risk of serious and nonserious bacterial and viral infections associated with the use of biologic therapy (abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab) in patients with rheumatoid arthritis (RA).

Methods

Information was derived from PubMed, EMBASE, and the Cochrane clinical trials register and database of systematic reviews and relevant congress abstracts up to and including February 2008.

Results

Compared with the general population, patients with RA have a heightened risk of infection, including tuberculosis. Long-term clinical trials and postmarketing studies indicate that anakinra and the tumor necrosis factor (TNF) inhibitors are associated with an increased risk of infections versus conventional disease-modifying antirheumatic drugs (DMARDs), especially early in the course of treatment. The most common sites of infection are the respiratory tract (including pneumonia), skin and soft tissue, and the urinary tract. The risk of tuberculosis also appears higher with TNF inhibitors (in particular, infliximab) versus DMARDs, although this can be reduced by screening and prophylaxis. TNF inhibitors do not appear to significantly increase the risk of reactivating chronic viral infections. Influenza and pneumococcal vaccinations are generally effective in the face of TNF inhibitors or abatacept. Available data suggest that the risk of infections and serious infections with abatacept and rituximab may be similar to that of the TNF inhibitors. To date, there have been no reports from clinical trials of increased tuberculosis or opportunistic infections with abatacept or rituximab.

Conclusions

All marketed TNF inhibitors for compared to control RA appear to increase the risk of serious and nonserious infections compared with DMARDs. Although suggestive, data for abatacept and rituximab are less definitive and longer periods of patient exposure to these agents are needed before an assessment of their risks can be made.

Section snippets

Methods

As a primary decision, only published data were considered for this review. Additionally, the decision was made to maintain the article as a review rather than a meta-analysis to permit a wider range of articles and abstracts of varying quality to be included. Potential limitations of this approach are acknowledged, where appropriate.

The primary information for this article was gathered from a search of the PubMed, EMBASE, and Cochrane (Clinical Trials Register and Systematic Reviews) databases

Discussion

This review of the literature on infections in patients receiving biological agents shows that our knowledge of this area is based on a mixture of results from randomized controlled trials, observational studies, and case reports of unequal quality. Furthermore, the literature is difficult to synthesize as a result of the heterogeneity of the populations and the widely different metrics used to present the data. Despite these substantial limitations, it is possible to draw certain conclusions

Acknowledgment

Support for third-party writing assistance for this manuscript, furnished by Neil Anderson, was provided by Genentech, Inc. and Biogen Idec.

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