Pooled RCTs: Adding LABAs to ICSs do not increase serious asthma events and reduce exacerbations

Peters, Jay I. MD
Maselli, Diego J. MD

University of Texas Health at San Antonio, San Antonio, Texas, USA

Source of funding: ICON Clinical Research.

For correspondence: Dr. W.W. Busse, University of Wisconsin Hospitals and Clinics, Madison, WI, USA. E-mail[email protected].

ACP Journal Club 169(10):p JC53, November 20, 2018. | DOI: 10.7326/ACPJC-2018-169-10-053

Question

In adolescents and adults with asthma, does adding long-acting β₂-agonists (LABAs) to inhaled corticosteroids (ICSs) affect risks for serious asthma events or exacerbations?

Scope

Planned pooled analysis of 4 randomized noninferiority trials (ClinicalTrials.gov NCT01444430, NCT01475721, NCT01471340, and NCT01845025) that compared ICS–LABAs with ICSs alone in adolescents ≥ 12 years of age and adults {who had asthma for ≥ 1 year, used daily asthma medication, and had ≥ 1 exacerbation in the past year but not in the past 4 weeks. Exclusion criteria included life-threatening asthma or smoking history of > 10 pack-years}. Recruitment in 1 trial was stopped early when the study drug was removed from the market. LABAs were formoterol and salmeterol; ICSs were budesonide, fluticasone, and mometasone. Primary outcome was a composite of asthma-related death or intubation. Secondary outcomes included individual components of the primary outcome, serious asthma-related events (death, intubation, and hospitalization), and asthma exacerbations.

Methods

Individual-patient data meta-analysis of 36 010 patients ({mean age 44 y}, 66% girls and women), with follow-up at 26 weeks. The meta-analysis was planned before the 4 trials were designed; data were analyzed using an intention-to-treat approach. Outcome adjudicators were blinded to group allocation.

Main results

For the primary outcome, there were 2 asthma-related deaths (ICS–LABA group) and 3 asthma-related intubations (1 in the ICS–LABA group); this outcome was considered not to have provided robust results. Results for serious asthma-related events and asthma exacerbations are in the Table.

Table. **Inhaled corticosteroids (ICSs) combined with long-acting β₂-agonists (LABAs) vs ICSs alone in adolescents and adults with asthma‡**
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Conclusion

In adolescents and adults with asthma, adding long-acting β₂-agonists to inhaled corticosteroids did not increase risk for serious asthma-related events and reduced exacerbations.