Forget expensive monoclonal antibody therapies, the future of treatment for severe asthma may lie in your everyday azithromycin.
A landmark Australian study has shown that 500mg of azithromycin taken three times per week led to a 40% reduction in severe attacks among patients with persistent uncontrolled asthma, compared with a placebo.
Commenting on the study, Professor Connie Katelaris, professor of Immunology and Allergy at the Western Sydney University, said macrolide therapy looked set to have a greater role in the next iteration of asthma guidelines.
“Many of us in clinical practice have been adding in macrolides for the three or four months of winter in some of these people with good effect, but now we’ve got evidence that it does indeed change their exacerbation rate and improve their control,” she said.
While the concept of using macrolides in asthma was not new, Professor Katelaris said the quality of this study was definitive in showing their efficacy.
The randomised controlled trial of 420 patients with uncontrolled persistent asthma used low dose azithromycin on top of the patients’ regular medium-to-high dose inhaled corticosteroids and long-acting bronchodilator therapy.
Over the 48-week trial, patients taking the antibiotic also experienced improved quality of life in addition to a decrease in asthma exacerbations.
Importantly, the researchers found the benefit occurred in people with different asthma phenotypes, Professor Katelaris noted.
“So drugs like mepolizumab are indicated for people with eosinophilic asthma, a certain form of inflammation, whereas the azithromycin has brought about benefit in both those with eosinophilic and those with non-eosinophilic asthma,” she said.
As a result, the patients with uncontrolled asthma who didn’t qualify for the newer monoclonal antibody therapies now had a useful therapy option, and one that was far cheaper than the roughly $900 per month monoclonal antibody therapies cost, she said.
Macrolides were known to have antibacterial, antiviral and anti-inflammatory effects, the authors explained. However, their study did not show evidence of an antibacterial effect and there was also no reduction in inflammatory cell counts in patients’ sputum, so the mechanism of action was still unclear, they said.
Lead author Professor Peter Gibson, from the Hunter Medical Research Institute, Newcastle said there was appropriate concern regarding extended antibiotic use, and while they found fewer infections in the treatment group, “the use of azithromycin needs to be selective, in order to prevent concerns about antibiotic resistance”.
As a result, it might be beneficial to limit the medication for use over the winter months in people with poorly controlled asthma, rather than keeping them on it all year round, Professor Katelaris said.
The antibiotics were well tolerated and side effects were minimal, except for some cases of diarrhoea. Nevertheless, patients still needed to be monitored and more orthodox treatments optimised, she added.
It was also worth noting the study excluded patients who had prolonged QT intervals and who had any hearing problems. Patients would need to be screened for these conditions in practice, Professor Katelaris said.
Lancet 2017; online 4 July