Safety of formoterol in asthma clinical trials: an update

Abstract

Use of long-acting b-agonists (LABAs) in asthma remains controversial, and large safety trials are in progress. We have previously reported safety outcomes with formoterol in 117 AstraZeneca asthma trials (78 339 patients, 92% using inhaled corticosteroids) completed by December 2006, and have now added 32 trials with formoterol (26 124 patients, 100% using inhaled corticosteroids) completed by December 2011.The primary dataset of 79 randomised controlled trials includes 94 684 patients, 67 380 of whom were exposed to formoterol, while the complete dataset comprises 149 trials and 104 463 patients. There were no new asthma-related deaths in the expanded primary dataset, with eight asthma-related deaths among formoterolrandomised patients and two among non-LABA-randomised patients (relative risk 1.13, 95% CI 0.23-10.9), and 15 versus nine cardiac-related deaths (relative risk 0.47, 95% CI 0.19-1.22). Nonfatal asthma-related serious adverse events were significantly reduced with formoterol (relative risk 0.63, 95% CI 0.53-0.75), as were discontinuations due to adverse events. Examining 40 trials with direct formoterol versus non-LABA comparisons, Mantel-Haenszel relative risk for asthma-related death was 2.75 (95% CI 0.52-14.4) and for serious adverse events 0.83 (95% CI 0.68-1.02).We conclude that this enlarged dataset indicates no increased risk of asthma-related deaths among patients exposed to formoterol compared with non-LABA treatments, although the wide confidence interval precludes certainty. @ERSpublications No increased risk of asthma-or cardiac-related deaths or serious adverse events associated with the use of formoterol http://ow.ly/qfShl For editorial comments see page 6.

Safety of β2-agonists: a 50-year debate closed?

“…The authors conclude that data on all-cause serious adverse events should be more fully reported in journal articles, and not combined with all severities of adverse events or limited to those events that are thought by the investigator to be drug-related [18]. The discrepancies between the SEARS and RADNER [16] study and the meta-analysis of CATES et al [18,19] are unclear since results are not similar. The outcomes studied may not be identical but it is surprising that SEARS and RADNER [16] did not compare their results with those of CATES et al [18,19].…”

“…The discrepancies between the SEARS and RADNER [16] study and the meta-analysis of CATES et al [18,19] are unclear since results are not similar. The outcomes studied may not be identical but it is surprising that SEARS and RADNER [16] did not compare their results with those of CATES et al [18,19].…”

“…One death in the salmeterol trials and eight in the formoterol trials limited the ability to measure risk for this outcome. In the study of SEARS and RADNER [16], statistical issues prevent the proposition of a definite conclusion. Finally, there are pitfalls in meta-analyses of RCTs [17].…”

“…The analysis included all AstraZeneca randomised controlled parallel-group asthma trials of 3-12-month duration involving formoterol [15]. The study of SEARS and RADNER [16] published in this issue of the journal expands the previous study completed in December 2006 and reports the results of around 100 000 patients followed up by AstraZeneca [15]. The relative risk of asthma-related deaths was 1.13 with formoterol (eight versus two; RR 1.13, 95% CI 0.19-1.22).…”

Drugs Efficiency and Safety: The Role of Pharmaceutical Industry

“…За-ключение другого мета-анализа аналогичных РКИ, проведенного участниками исследования SMART с конфликтом интересов заметно отличается: «Салмете-рол в комбинации с ингаляционными кортикостерои-дами снижает риск тяжелых обострений астмы, не из-меняет риск госпитализаций по поводу астмы и, воз-можно, не изменяет риска смерти от астмы или инту-бации по сравнению с лечением только ингаляционными кортикостероидами» [21]. Различия в заключениях мета-анализов исследований, выполненных незави-симыми и зависимыми от производителя исследова-тельскими группами, обнаружены у другого ингаля-ционного пролонгированного бета2-агониста -фор-мотерола [22,23].…”