Clinical research studyThe Comparative Safety of Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta-analysis Update of 44 Trials
Section snippets
Data Sources and Searches
Study selection, assessment of eligibility criteria, data extraction, and statistical analysis were performed on the basis of a predefined, peer-reviewed protocol according to the Cochrane Collaboration guidelines (http://www.cochrane.org/resources/handbook/index.html).
We undertook a systematic literature search including randomized controlled trials that selected adult patients with rheumatoid arthritis. We searched studies using MEDLINE via OVID and PubMed, the Cochrane databases, Google
Study Selection
We identified a total of 268 titles and abstracts, from which 195 were excluded on the basis of title and abstract review and 31 were excluded on the basis of article review (Figure 1). Reasons for exclusion included no drug of interest; patients without rheumatoid arthritis; lack of randomization, blinding, or a control group; or a study duration <12 weeks (Appendix 2, available online shows a list of excluded studies). A total of 44 studies, including 3 studies obtained from PubMed Auto Alert
Discussion
Our objective was to systematically update major safety profiles reported in the randomized controlled trials of all approved tumor necrosis factor inhibitors to date to inform the field. Our findings indicate a higher risk of serious infection associated with adalimumab, certolizumab pegol, and infliximab, which seems to contribute to higher rates of discontinuation. A similar trend was observed with golimumab plus methotrexate combination therapy, but not golimumab monotherapy. In contrast,
Conclusions
Our meta-analysis of randomized controlled trials to date indicates potential important differences in the safety profile among all currently available tumor necrosis factor inhibitors. The risk of serious infection is increased among adalimumab-, certolizumab pegol–, or infliximab-treated patients. In turn, patients taking these agents had an increased risk of discontinuation due to adverse events. Etanercept-treated patients instead showed a decreased risk. Our null findings on malignancy
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Funding: This research was supported by the National Institutes of Health (RC1AR058601).
Conflict of Interest: None.
Authorship: All authors had access to the data and played a role in writing this manuscript.