Rates of serious infections, opportunistic infections, inflammatory bowel disease, and malignancies in subjects receiving etanercept vs. controls from clinical trials in ankylosing spondylitis: a pooled analysis

Abstract

Objectives: Therapies involving anti-tumour necrosis factor are associated with increased risk of serious infections, opportunistic infections, and some types of malignancies in subjects with rheumatic diseases. However, limited data have been collected for subjects with ankylosing spondylitis (AS). The aim of this retrospective analysis of all sponsor-conducted trials was to examine the rates of serious infections, inflammatory bowel disease (IBD), malignancies, and non-malignant skin cancers during treatment in subjects with AS.

Method: Data from five randomized controlled trials (one sulfasalazine-controlled, four placebo-controlled) and four open-label studies evaluating etanercept were pooled for analyses. All randomized subjects who received at least one dose of treatment were included in the study.

Results: Analyses included 1323 subjects (> 1500 subject-years of treatment). Rate ratios of serious infections and IBD events for etanercept vs. placebo/sulfasalazine during the double-blind studies were 2.19 [95% confidence interval (CI) 0.22–107.79] and 1.09 (95% CI 0.06–64.56), respectively. There were no reports of opportunistic infections. Using the Surveillance, Epidemiology and End Results database, the standardized incidence ratio for malignancies was 1.47 (95% CI 0.54–3.21).

Conclusions: These data suggest that etanercept is well tolerated in subjects with AS. Despite the large number of patients, the 95% CI data all cross 1.0, limiting possible conclusions. No new safety signals were observed.

Acknowledgements

The studies described here were funded by Wyeth, which was acquired by Pfizer Inc in October 2009, and by Amgen. The authors would like to thank Craig Wagerle, PhD of Pfizer Inc for assisting with data collection and analysis. Medical writing support was provided by Patricia McChesney and Joseph Ramcharan of Engage Scientific Solutions and was funded by Pfizer Inc.

Supporting Information

Additional Supporting Information may be found in the online version of this article.

Supplementary Table 1. Search terms used to identify inflammatory bowel disease events, serious infections, and opportunistic infections.

Supplementary Table 2. Baseline demographics and characteristics by study, double-lind studies only (open-label extension studies excluded).

Supplementary Figure S1. Nine studies used for pooled analysis.

Supplementary Figure S2. Time to first inflammatory bowel disease (IBD) event.

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