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.

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.

Sustained efficacy and safety, including patient-reported outcomes, with etanercept treatment over 5 years in patients with ankylosing spondylitis.

OBJECTIVES: To assess long-term safety and clinical efficacy of etanercept 25 mg subcutaneously twice weekly up to 5 years in subjects with ankylosing spondylitis (AS). METHODS: An open-label (OL), multicentre, phase 4, 156-week extension study of subjects with AS who had completed a 12-week randomised, placebo-controlled study (N=84; n=45 etanercept, n=39 placebo) followed by a 96-week OL study (n=81; n=42 etanercept/etanercept; n=39 placebo/etanercept); 59 subjects who completed the 96-week OL extension enrolled in the current OL trial and continued etanercept 25 mg BIW for an additional 156 weeks (total duration: 264 weeks, original etanercept group; 252 weeks, original placebo group). Safety was based on spontaneous reports of adverse events (AEs). Last observation carried forward was used for imputation of missing values. RESULTS: Thirty-seven of 59 subjects (63%) completed 5 years of etanercept treatment. Serious non infectious AEs and serious infections occurred at a rate of 0.17 and 0.03 events per subject years, respectively; inflammatory bowel disease and uveitis (including iritis and iridiocyclitis) occurred at 0.01 and 0.14, respectively. No cases of tuberculosis or opportunistic infections were reported. Assessment in Ankylosing Spondylitis (ASAS) responses and improvements in Bath Ankylosing Spondylitis Functional Index and spinal mobility were sustained from week 108 through week 264. CONCLUSIONS: Etanercept was well tolerated with no new safety signals detected in subjects with AS over 5 years. Clinical efficacy and improvements in function and mobility seen during the double-blind and first OL study were sustained. These results support etanercept therapy for the long-term management of this chronic disease.