Inhaled steroids with and without regular formoterol for asthma: serious adverse events

Area of Science:

• Pulmonology and Respiratory Medicine
• Clinical Pharmacology
• Evidence-Based Medicine

Background:

• Epidemiological studies suggest a link between beta2-agonists and increased asthma mortality.
• Debate exists regarding the safety of regular long-acting beta2-agonists (LABA) when combined with inhaled corticosteroids (ICS).
• This Cochrane Review is an update incorporating data from large trials mandated by the US FDA.

Purpose of the Study:

• To evaluate the risk of mortality and serious adverse events (SAEs) in chronic asthma patients.
• To compare outcomes in participants randomly assigned to regular formoterol and ICS versus ICS alone.

Main Methods:

• Systematic review and meta-analysis of randomized controlled trials (RCTs).
• Inclusion criteria: parallel-design RCTs of adults and/or children with asthma, treated for at least 12 weeks.
• Data extraction included unpublished trial data on mortality and SAEs; confidence in evidence assessed using GRADE.

Main Results:

• Adults: No significant difference in all-cause mortality (OR 1.25, 95% CI 0.61-2.56, moderate-certainty) or asthma-related deaths (low-certainty).
• Adults: No difference in non-fatal SAEs (OR 1.00, 95% CI 0.87-1.16, high-certainty).
• Children/Adolescents: No deaths reported; SAEs showed no significant difference (OR 1.33, 95% CI 0.71-2.49, moderate-certainty), though numbers were small.

Conclusions:

• No significant difference in mortality or non-fatal SAEs was found for adults using formoterol with ICS versus ICS alone.
• The risk of death in both groups was very low, but certainty of evidence for mortality difference is low.
• Clinical decisions should balance symptomatic benefits of formoterol/ICS with potential uncertainties regarding harmful effects, especially considering limited data in children.