A systematic review and meta-analysis of 27 clinical trials has found that two combination inhalers used to treat asthma are both superior to inhalers containing only a short-acting beta agonist (SABA) in reducing the risk of severe asthma flare-ups and improving symptoms. The study showed that combined inhaled corticosteroids (ICS) plus formoterol reduced the risk of severe asthma symptom flare-ups by 10.3 per cent compared to SABA alone, while combined ICS plus SABA reduced this risk by 4.7 per cent.
Asthma is a very common chronic respiratory illness that affects 262 million people worldwide. In some people with asthma, symptoms can be so severe that they may require hospitalization. Symptoms can even be fatal in extreme cases. Most cases of mortality associated with asthma are preventable through medications, but not all asthma medications are equally effective.
SABAs, such as salbutamol, are a type of bronchodilator that have traditionally been used to treat asthma. These medications quickly relieve asthma symptoms by opening the airways. For many years, SABAs were the only form of treatment that many people with asthma received. However, researchers have begun to rethink SABAs in recent years.
“SABAs provide temporary relief in the moment,” said Dr. Derek Chu, lead author of the study. “It’s like taking an ibuprofen for a fever: it might help you get through it, but it doesn't actually fix the reason why you have a fever in the first place. For many years, we've thought that asthma is a problem of the airways getting squeezed down, and if we can open the airways with SABAs then people will feel better. Since then, we’ve found that inflammation is a key part of asthma and that it is a major cause of airway constriction and severe asthma flare-ups.”
Dr. Chu (pictured) is an affiliate scientist at the Firestone Institute for Respiratory Health – a partnership between St. Joseph’s Healthcare Hamilton and McMaster University – as well as an assistant professor in the departments of medicine and health research methods, evidence, and impact (HEI) at McMaster.
“What this study specifically addresses is whether combination treatments that include a reliever and an anti-inflammatory drug are more effective than opening the airways alone with SABAs,” said Dr. Chu, “and if so, what's the most effective anti-inflammatory reliever to use?”
Inhaled corticosteroids (ICS) are a type of medication that reduces airway inflammation to help manage asthma symptoms and reduce the risk of symptom flare-ups. SABAs quickly open the airways. Another reliever is called formoterol – a long-acting version of a SABA that works by opening the airways just like SABAs do. Given the many choices, scientists like Dr. Chu have been working to help people living with asthma and their physicians choose the most effective medication.
Through a comprehensive meta-analysis, Dr. Chu and his team analyzed 27 randomized controlled trials that examined the patient outcomes of ICS and SABA, and ICS and formoterol combinations when compared to reliever-only (SABA) treatments. The studies analyzed included a total of 50,496 patients.
These results have the potential to inform healthcare guidelines and policies around the world and influence which asthma medications patients can access.
“The United States has released a combination inhaler that includes both ICS and SABA medication,” said Dr. Chu. “Now, other places around the world are wondering whether they should use it. In addition, ICS and formoterol combinations have been approved in a few locations to control asthma, but they have not been consistently approved as a reliever. The superiority of both anti-inflammatory relievers over SABA only relief, bronchodilation only without addressing underlying inflammation, should stimulate updated clinical practice guidelines and policy, including insurance coverage.”
As this meta-analysis is the first to compare different studies on the effectiveness of combined ICS and SABA, and ICS and formoterol asthma treatments, it can also function as a guidepost for how future studies in this area are designed. Dr. Chu’s research has created an opportunity for many other asthma researchers to further bolster the evidence behind combination anti-inflammatory and reliever treatments for asthma symptom management.
Funding was provided by the American Academy of Allergy, Asthma, and Immunology (AAAAI) and American College of Allergy, Asthma and Immunology (ACAAI) through the Joint Task Force on Practice Parameters to inform upcoming guidance on the management of severe asthma.
The study was published in JAMA on October 28, 2024 and coordinated with the ACAAI Annual Meeting Plenary Presentation.