Adult bronchiectasis, asthma therapy, frailty in ILD

Airways Disorders

ICS/LABA combo therapy: black box warning removed

Publication of the Salmeterol Multicenter Asthma Research Trial (SMART) in 2006 caused panic among asthmatics and the physicians who treat them (Nelson et al. Chest. 2006;129[1]:15). The study suggested that the long-acting beta-2-agonist (LABA) salmeterol leads to an increased risk of asthma/respiratory-related deaths compared with placebo. This finding was more pronounced in the African American subpopulation. The study left many questions unanswered, including whether or not this risk is present when LABA therapy is combined with inhaled corticosteroids (ICS) (O’Byrne. Chest. 2006;129[1]:3). Subsequent meta-analyses confirmed the increased risk with LABA monotherapy but not with LABA/ICS (Salpeter et al. Ann Inter Med. 2006;144[12]: 904; Jaeschke et al. Am J Respir Crit Care Med. 2008;178[10]:1009). Still, a black box warning relating LABA to asthma-related death was applied to LABA/ICS products.

In 2011, the Food and Drug Administration (FDA) mandated large, randomized controlled trials be performed for LABA/ICS products to assess safety. These trials were recently completed, showing no difference in asthma-related deaths between LABA/ICS and ICS alone. There were 41, 297 patients across four trials, three included teenagers and adults (age ≥ 12) and one enrolled children (ages 4-11). These studies prompted the FDA to remove the black box warning from salmeterol/fluticasone, formoterol/budesonide, and formoterol/mometasone (https://wwwfdagov/downloads/Drugs/DrugSafety/UCM589997pdf).

Conclusion: Because LABA/ICS therapy is effective for asthma, most pulmonologists continue to prescribe it despite the SMART study results and FDA warning. In a practical sense, we don’t expect the FDA findings to radically change asthma care. Still, it seems we can finally put this question to rest – LABA/ICS is indeed safe for asthmatics. Most physicians will continue to avoid LABA monotherapy, and now that tiotropium is included in the 2017 GINA guidelines, it’s only matter of time before we’re debating whether LABA/long-acting muscarinic antagonist (LAMA) is safe for asthmatics.

Aaron Holley, MD, FCCP
Steering Committee Member

Navitha Ramesh, MD, MBBS
Fellow-in-Training Member