More on the safety of LABA

Paul O’Byrne, Roman Jaeschke

Related McMaster Perspective episodes

O’Byrne P, Jaeschke R. Safety of LABA: Current state of knowledge.
O’Byrne P, Jaeschke R. Safety of LABA: A little bit of history.


Peters SP, Bleecker ER, Canonica GW, et al. Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. N Engl J Med. 2016 Sep 1;375(9):850-60. doi: 10.1056/NEJMoa1511190. PubMed PMID: 27579635.
Stempel DA, Szefler SJ, Pedersen S, et al; VESTRI Investigators. Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma. N Engl J Med. 2016 Sep 1;375(9):840-9. doi: 10.1056/NEJMoa1606356. PubMed PMID: 27579634.
Stempel DA, Raphiou IH, Kral KM, et al; AUSTRI Investigators. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. N Engl J Med. 2016 May 12;374(19):1822-30. doi: 10.1056/NEJMoa1511049. PubMed PMID: 26949137.

Roman Jaeschke: Welcome to another edition of McMaster Perspective. We have recently had an interview with the Chief of Department of Medicine at McMaster University, Professor O’Byrne, who in the meantime became the Dean of the [Michael G. DeGroote] School of Medicine, for which I would like to congratulate you.

Paul O’Byrne: Thank you very much, Professor Jaeschke.

RJ: In the meantime, we got 2 new papers on the use of inhaled corticosteroids (ICSs) and long-acting ß2-agonists (LABAs) in patients with asthma. Our previous review started from SMART studies and some concerns about the use of LABAs. We went through the history, now we have an update. Professor O’Byrne…

PO: In the New England Journal of Medicine relatively recently there were 2 new studies published, both of which were 26-week studies evaluating the safety of adding a LABA to an inhaled steroid compared to an inhaled steroid alone in patients who were inadequately controlled at the time of entry into the trial. Each of these studies was relatively large, in the region of 10,000 to 12,000 patients.

In one study, children were evaluated with a combination consisting of fluticasone, which is the inhaled steroid, and salmeterol, the inhaled LABA. This was done because that combination has been approved for use in childhood asthma. In the second study, a different combination of inhaled steroids and LABA was budesonide and formoterol, a combination known as Symbicort. That study was done in adults; again, around 11,000 patients studied over 26 weeks.

The studies were designed to evaluate safety. There was a composite measure that was used to assess safety, which were deaths from asthma, hospitalizations, or intubations requiring intensive care because of acute severe asthma events. Neither study showed any signal in relation to increased risk of severe adverse events associated with the addition of the inhaled LABA to the steroid and both showed some benefit in relation to reducing the risk of severe asthma exacerbations.

Both of these studies are part of a series of studies – there will be 4 studies completed in total – which has looked at the various combinations of ICS-LABA in adults, of which 3 of the studies will be done, and this one in children. One study, previously reported by David Stempel and colleagues, had looked at the fluticasone-salmeterol combination in adults and again showed no evidence of a safety signal. The only study remaining, which is just about to be completed, looks at the combination of mometasone and formoterol, which is another ICS-LABA combination approved for use in North America, and in fact worldwide.

In summary, these 3 studies taken together show very reassuring evidence that the use of a LABA added to an inhaled steroid is safe and also does provide clinical benefit in reducing severe exacerbation risk.

RJ: A practical question: if the patient reads on the internet that there is a concern about LABA or there was a concern about LABA and comes to your asthma clinic and says, “Professor O’Byrne, you are prescribing me now the combination treatment, I have heard that it may be harmful,” what would you say to them?

PO: That is a very important question to ask because each of these combinations does have a label warning, a box warning, about their safety; particularly in the United States, where public advertising is allowed for medications, these warnings are very clearly described in this – mainly television – advertising. Patients do pick up on that, and they should. I find these studies looked at as a whole very reassuring and I will – and I have – use this evidence to reassure my patients that despite concerns being raised about the safety of these combinations, these very large safety studies, designed in a way to formally look at the safety of these medications, have shown them to be not only efficacious but very safe.

RJ: Thank you very much. I hope this is useful to our viewers. Thank you.

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