Both Symbicort and Advair contain drugs called long acting beta-agonists, or LABAs for short. Symbicort contains formoterol and Advair contains salmeterol. Advair and Symbicort also contain inhaled corticosteroids(ICS), fluticasone and budesonide, respectively. This combination of medications has been repeatedly shown in multiple prospective, randomized placebo-controlled trials to improve symptoms, lung function, and quality of life in asthmatics. More importantly, combination ICS/LABA medications have been shown to reduce asthma exacerbations. So what’s the problem?
The problem is, there are now two large meta-analyses which have shown an increased risk of adverse events in patients receiving LABAs. A meta-analysis pools data from multiple trials in order to achieve higher statistical power. These meta analyses have serious limitations, however.
The first meta analysis was published by Dr. Shelley Salpeter, a primary care physician, in June, 2006. It examined the use of salmeterol. Among the co-authors were her father, an astrophysicist, and her son, then a high-school student. Remarkably, and somewhat disconcertingly, the study was published in the Annals of Internal Medicine, one of the most rigorous and respected journals in the field. It set off a firestorm of controversy in the asthma community and was roundly panned. The primary flaw in the Salpeter paper was the large number of patients who came from the inaptly named SMART trial, where subjects were not required to utilize ICS along with their salmeterol. That is a big no-no. Not surprisingly, the majority of serious adverse events in the meta-analysis came from the SMART trial. A follow-up meta-analysis published by respected asthma physicians Hal Nelson and Jean Bousquet, among others, confirmed what previous trials had shown- patients receiving combination ICS/LABA medications have fewer exacerbations and no increased risk for serious adverse events.
Now, a new meta-analysis has come out examining formoterol. Apparently, the authors have not boned up on their recent history, because they repeat the same fatal flaw of the Salpeter paper- they included subjects who were not required to utilize ICS concomitantly with their LABA. Predictably, the results are similar. The shock value headline will read, “57% increase in serious non-fatal events!”, but the reality is that for every 1000 asthma patients in the analysis, 16 formoterol patients had a serious event and 10 placebo patients had a serious event, so the absolute risk increase is only 0.6%. Additionally, the meta-analysis does not tell us whether those 6 extra patients were on formoterol alone or in combination or what dose of formoterol was used.
The take home message is this: if your asthma is bad enough to require combination ICS/LABA therapy, then you can be reassured that there a wealth of data and experience supporting their effectiveness and safety.
Disclaimer: I have no financial ties to either GlaxoSmithKline(Advair) or AstraZeneca(Symbicort), or to any other pharmaceutical company for that matter. On occasion, I eat a grilled chicken salad at lunch with a GSK rep.