Most Cochrane Reviews seek to cover both the benefits and harms of interventions, but the complexity of the research on the adverse effects of some treatments means that a few reviews are dedicated to just the potential harms. One of these, on one of the drugs used for treating asthma was updated in September 2019, and lead author, Sadia Janjua from Cochrane Airways at St. George's, University of London in the UK, tells us about the latest findings in this podcast.
The standard treatment for people with asthma is a low-dose inhaled corticosteroid. But if this does not control their asthma on its own, many guidelines recommend adding a long-acting beta₂-agonist, or LABA. Our focus is one of drugs in this class of drugs, formoterol. §
LABA, such as formoterol, have the advantage of longer duration of action than short acting beta- agonists, which means that they can be taken twice daily and used alongside inhaled steroids for regular maintenance treatment for people with persistent asthma symptoms. There has been, however, some apprehension about using LABA as long-term maintenance treatment because they may mask symptoms of deteriorating asthma, which could delay treatment for severe exacerbations. In turn, this could increase the risk of asthma-related deaths. LABAs may also lead to tolerance to their bronchodilator effects when used long-term.
The concerns over safety led the American Food and Drug Administration to commission large trials to assess the safety of the combination of a LABA and a corticosteroid when given together in a single inhaler as regular treatment for adults with asthma. These trials have now been published and we updated our review of serious adverse effects in children and adults taking formoterol in combination with an inhaled corticosteroid, to incorporate the new results. This has given us more information to assess whether this combination is safe in the long term and although we have found no evidence that it’s not safe, some uncertainty remains.
Following the recent trials, the FDA removed the black triangle from its guidance on LABAs, showing that they consider the long-term use of LABA with an inhaled corticosteroid to be safe. And, looking at the research evidence, we’ve not found any long-term safety concerns (such as an increased risk of dying from asthma) when the results of the new studies are combined with the information from earlier trials which was already in the 2017 version of the review. However, it needs to be noted that this reassurance comes from trials in which treatment with formoterol and corticosteroid was usually well supervised. Moreover, there were very few deaths from asthma in any of the trials. Just three adults out of 13,000 on regular formoterol and inhaled corticosteroid died of asthma and none of 11,000 on the steroid alone die during the trials, and there were no deaths in children.
So, even with the evidence from the large new trials, the very small number of deaths does not allow us to say for sure that there is no additional risk when formoterol is given regularly in combination with an inhaled corticosteroid. Therefore, it might be best to assess the benefits of regular combination treatment for people with asthma on an individual level and, if symptom control is clearly improved, then this may outweigh the fact that we cannot completely rule out any increase in the risk of harm.