Recent research reveals that anti-inflammatory inhalers not only cut the risk of severe asthma complications but also offer modest improvements in symptom control compared to traditional bronchodilator treatments.
Study: Inhaled Reliever Therapies for Asthma. Image Credit: Viktoria Ostroushko/Shutterstock.com
In a recent study published in the JAMA, a group of researchers evaluated and compared the effectiveness of short-acting β agonists (SABA) alone versus SABA combined with inhaled corticosteroids (ICS) and formoterol combined with ICS in managing asthma symptoms and reducing complications.
Background
Asthma affects approximately 262 million people worldwide and is characterized by airway inflammation and variable airflow obstruction. Reliever inhalers, including SABA like albuterol and ICS combined with SABA or formoterol, are used to alleviate symptoms such as dyspnea, wheezing, and cough.
Although guidelines recommend ICS-formoterol as a preferred reliever over SABA alone, the recent US Food and Drug Administration (FDA) approval of ICS-SABA has created confusion regarding the optimal choice of reliever. Further research is needed to clarify the comparative benefits of ICS-SABA and ICS-formoterol on clinical outcomes in asthma management.
About the study
The present prospectively registered systematic review (PROSPERO) adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
A systematic search of the Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was conducted from January 1, 2020, to September 27, 2024, focusing on published and unpublished randomized clinical trials (RCTs) evaluating inhaled reliever therapies for asthma.
The review included various inhaled reliever therapies, such as SABA, and combinations of ICS with SABA or formoterol.
Reviewers independently screened titles, abstracts, and full texts using standardized forms for data extraction. Based on input from a multistakeholder guideline development group, outcomes encompassing asthma symptom control, quality of life, severe complications, and adverse events were prioritized.
The risk of bias for each study was assessed using a modified Cochrane Risk of Bias tool. Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, classifying evidence as high, moderate, low, or very low based on various factors.
Data synthesis involved pairwise effect estimates through random-effects meta-analyses, with publication bias assessed via funnel plots and trial registries.
Study results
The systematic search resulted in 3,179 unique citations and identified 201 potentially relevant full articles. Ultimately, 26 articles were included, reporting on 27 unique RCTs involving a total of 50,496 patients. The participants in these trials had a mean age of 41.0 years, with male participants making up a median of 41%.
The treatment duration varied, with a median of 26 weeks across studies. All RCTs involving fast-onset, long-acting β agonists evaluated formoterol, and two trials specifically focused on populations of patients aged 18 years or younger.
All trials were conducted in outpatient settings, and oral corticosteroid prescriptions for severe exacerbations were at the physician's discretion.
Among 138 assessments of risk of bias for study outcomes, 113 (82%) indicated a low overall risk of bias. Visual inspections of funnel plots and evaluations of potential effect modifiers showed no significant evidence of small study effects or network incoherence.
For severe complications, data from 22 RCTs involving 45,117 patients indicated that ICS-formoterol significantly reduced the risk of severe complications compared to bronchodilator-only relievers, with a risk ratio of 0.65. ICS-SABA also showed a lower risk of severe complications with a risk ratio of 0.84.
In terms of asthma symptom control, 22 RCTs involving 25,233 patients demonstrated that both ICS-formoterol and ICS-SABA were associated with slight improvements in symptom control compared to bronchodilator-only relievers. However, these improvements may be clinically insignificant. For asthma-related quality of life, moderate-certainty evidence suggested minimal increases in quality of life scores associated with both ICS-formoterol and ICS-SABA.
Safety analyses involving 12 RCTs for any adverse events indicated no significant increase in harm among inhaler groups. For serious adverse events, 23 RCTs were reviewed, with common reports including cardiovascular events and pneumonia. Subgroup analyses showed consistent results across various demographics and asthma types, confirming the reliability of the findings.
Conclusions
To summarize, this systematic review and meta-analysis involved 27 randomized clinical trials with 50,496 adult and pediatric asthma patients. It provided high-certainty evidence that anti-inflammatory reliever treatments with ICS-formoterol and ICS-SABA (whether combined or separate inhalers) significantly reduced the risk of severe complications.
Additionally, these treatments offered modest improvements in asthma symptom control compared to bronchodilator-only relievers. Both anti-inflammatory strategies did not show a statistically significant difference in adverse event risk.
While ICS-formoterol was likely associated with lower risks of severe complications compared to ICS-SABA, it may not lead to significant improvements in asthma symptoms or quality of life. This review notably utilized a comprehensive search strategy and included trials not covered in previous reviews.
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