A fixed-dose 2 in 1 combination of salbutamol and budesonide, used as an as-needed rescue medicine, has been shown for the first time to significantly reduce the risk of severe asthma attacks.
In the MANDALA trial, patients using the investigational AstraZeneca and Avillion product PT027, which combines salbutamol (marketed as albuterol within the U.S.) with budesonide, were 26% less likely to experience severe asthma attacks than those using albuterol alone.
These findings were reported by lead author Professor Alberto Papi, of the University of Ferrara in Italy, and colleagues, including Professor Richard Beasley, director of the Medical Research Institute of New Zealand (MRINZ), published in the New England Journal of Medicine on Sunday 15 May, and presented this week at the American Thoracic Society (ATS) 2022 International Conference.
Asthma is a chronic respiratory disease that affects more than 330 million adults and children worldwide, including over 610,000 in Aotearoa New Zealand, where we have one of the highest rates of asthma in the world. Reducing the risk of asthma attacks is the number one priority for the management of asthma in New Zealand and internationally. As a result, the findings from the MANDALA trial are of both local and global importance.
In asthma, inflammation of the airways in the lungs is central to both symptoms and asthma attacks. For more than 50 years, people with asthma were prescribed a short-acting beta2-agonist reliever inhaler such as salbutamol as the first-line treatment for symptom relief. However, while these reliever asthma inhalers are effective in reducing acute symptoms, they do nothing to alleviate the underlying inflammation responsible for those symptoms, leaving patients at risk of severe attacks, which can be life-threatening, resulting in hospitalisation and risk of death.
The idea behind the 2 in 1 combination reliever therapy approach is that by adding an anti-inflammatory preventer medication to the reliever inhaler, it allows the patient to self-titrate the dose of the preventer medication according to their changing needs, directly treating the underlying increase in airways inflammation that causes worsening symptoms.
Over the last decade, the 2 in 1 combination reliever therapy approach has been established in clinical practice worldwide with a different combination of the fast-onset and longer acting beta2-agonist formoterol with the preventer medication budesonide.
Landmark clinical trials undertaken by Professor Richard Beasley and the research team at the MRINZ have shown that a 2 in 1 inhaler containing budesonide and formoterol, is far more effective than the traditional single reliever inhaler such as salbutamol or terbutaline. These MRINZ studies have contributed to the evidence on which the Asthma and Respiratory Foundation of New Zealand adolescent and adult asthma guidelines recommend budesonide-formoterol, rather than salbutamol, as the preferred reliever medication, across the range of asthma severity.
Professor Richard Beasley, MRINZ director and MANDALA study co-author says, "The latest findings are of major clinical importance, as they provide further evidence that the 2 in 1 reliever therapy approach is superior to the historical single reliever therapy approach with medications such as salbutamol. Furthermore, it means there will soon be alternative products available for the 2 in 1 reliever therapy approach, with some doctors and patients likely to prefer the budesonide-salbutamol inhaler to the budesonide-formoterol inhaler.”
“The combined 2 in 1 inhaler reliever therapy approach is considered the biggest paradigm advance in the management of asthma for decades. Its widespread implementation in clinical practice provides a real opportunity to reduce the enormous global health burden from asthma,” says Professor Beasley.