medwireNews: Combining an inhaled corticosteroid (ICS) reliever with the fast-onset, long-acting β agonist formoterol or the short-acting β agonist (SABA) bronchodilator-only reliever lowers the risk for severe exacerbations in people with asthma, versus treatment with a SABA alone, indicate the findings of a systematic review.
The ICS reliever combinations were also associated with improved asthma control, as measured using the Asthma Control Questionnaire, compared with SABA-only treatment, with a high degree of evidential certainty, report the researchers in JAMA.
“The optimal asthma reliever remains unclear,” to date, remark Derek Chu (McMaster University Medical Centre, Hamilton, Ontario, Canada) and colleagues, adding that “guideline recommendations do not sufficiently differentiate between ICS-SABA and SABA-alone relievers.”
The investigators analyzed results from 27 randomized controlled trials (RCTs) including 50,496 adults and children with asthma (41% male) who all received inhaled reliever treatment. The team found consistent associations in both adult and pediatric populations.
Treatment approaches included a SABA only, ICS plus formoterol, and ICS plus a SABA.
Study outcomes included asthma symptom control, asthma-related quality of life, severe asthma exacerbations and their individual components (eg, use of systemic corticosteroids, hospitalizations), adverse events, and overall mortality.
Chu and colleagues classified trial results as being of high, moderate, low, or very low certainty (quality) evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE), where risk for bias, imprecision, inconsistency, and incoherence lead to down-grading.
ICS plus formoterol reduced the risk for severe asthma exacerbations by a significant 35% (–10.3% absolute risk difference) compared with a SABA-only, report Chu et al, with a high-certainty GRADE classification.
Furthermore, an ICS plus SABA reliever was associated with a significant 16% lower risk for severe exacerbations compared with SABA-only treatment, giving an absolute risk difference between the two methods of –4.7%, and this was based on high-certainty evidence. Asthma-related hospitalizations and emergency-department visits held similar associations, note the researchers.
ICS plus formoterol also reduced the risk for severe asthma exacerbations compared with ICS plus SABA, by a significant 22% (absolute risk difference of –5.5%), but this finding was only of moderate certainty.
From the 22 trials that evaluated asthma symptom control in 25,233 individuals, high-certainty evidence showed that both ICS plus formoterol and ICS plus SABA improved control compared with a SABA alone, with respective 1.07- and 1.09-fold increased chances of improving participants’ scores on the 5-point Asthma Control Questionnaire by at least 0.5 points. However, “these effect sizes were small and potentially unimportant to patients,” note Chu and team.
Similar, low-effect size results emerged in the five trials evaluating asthma-related quality of life where, compared with a SABA alone, ICS plus formoterol and ICS plus SABA were “likely” associated with greater improvements, “albeit by small amounts” and with only moderate-quality evidence, note the researchers.
Regarding treatment safety, the study team observed no increased risk for adverse events among inhaler treatment groups. The two most commonly reported serious adverse events in the 12 studies that evaluated them – with moderate certainty – were cardiovascular events, with absolute risk differences of –0.2% for both ICS plus formoterol versus a SABA alone and ICS plus SABA versus a SABA alone, and pneumonia, with corresponding risk differences of 0.1% and 0.2%.
“In this meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone,” conclude the study authors.
As a potential limitation of their analysis, the researchers note that none of the studies included directly compared ICS plus formoterol with ICS plus SABA. A large randomized controlled trial comparing these two inhalers could change the current results and findings, acknowledge Chu et al.
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