Safety of β2-Agonists in Asthma: Linking Mechanisms, Meta-Analyses and Regulatory Practice

The AAPS Journal
Sanjeeva Dissanayake

Abstract

An epidemic of asthma fatalities in the 1970s prompted a series of case-control studies which indicated that short acting β-agonists increased the risk of death. Subsequent mechanistic and pharmacodynamic studies have suggested that β-agonist monotherapy facilitates airway inflammation, although when co-administered with inhaled corticosteroids (ICSs), similar evidence is lacking. The Salmeterol Multicenter Asthma Research Trial, which revealed a fourfold increase in asthma-related deaths in salmeterol-treated patients, prompted a paradigm shift in the evidential assessment of β-agonist safety. The FDA's meta-analysis of over 60,000 patients ultimately concluded that long-acting β-agonist (LABA) therapy increased the risk of serious asthma-related events. However, this meta-analysis itself raised questions given a large body of omitted data and a limited emphasis on the risk of ICS-LABA co-administration. Subsequently, the FDA mandated the conduct of five large studies to definitively ascertain whether ICS-LABAs increase asthma-related risk. Whether this ambitious programme will provide certainty remains to be seen given issues of multiplicity, the very low frequency of fatal and near-fatal asthma, and the administration of a f...Continue Reading

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Citations

Jun 3, 2018·Therapeutic Advances in Respiratory Disease·Anna PłoszczukSanjeeva Dissanayake
Oct 31, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Miranda Sin-Man TsangChun-Kwok Wong
Nov 29, 2020·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Andrea Biancoparticipants of the regional meetings

Related Concepts

Salmeterol
Proventil
Asthma
Forced Expiratory Volume Function
Glucocorticoid Effect
Research Methodology
United States Food and Drug Administration
Meta Analysis (Statistical Procedure)
Anti-Asthmatic Agents
Adrenergic beta-2 Receptor Agonists

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