Application of Multicategory Exposure Marginal Structural Models to Investigate the Association between Long-Acting Beta-Agonists and Prescribing of Oral Corticosteroids for Asthma Exacerbations in the Clinical Practice Research Datalink

摘要

Objective: To examine the comparative effectiveness of inhaled long-acting beta-agonist (LABA), inhaled corticosteroid (ICS), and ICS/LABA combinations. Methods: We used a retrospective cohort design of patients older than 12 years with asthma diagnosis in the Clinical Practice Research Datalink to evaluate asthma-related morbidity measured by oral corticosteroid (OCS) initiation within 12 months of initiating LABAs, ICSs, or ICSs/LABAs. Asthma severity 12 months before drug initiation (use of OCSs, asthma-related hospital or emergency department visits, and number of short acting betaagonist prescriptions) and during follow-up (short-acting betaagonist prescriptions and total number of asthma drug classes) was adjusted as a time varying variable via marginal structural models. Results: A total of 51,103 patients with asthma were followed for 12 months after receiving first prescription for study drugs from 1993 to 2010. About 92 initiated ICSs, 1 initiated LABAs, and 7 initiated ICSs/LABAs. Compared with ICSs, LABAs were associated with a 10 increased risk of asthma exacerbations requiring short courses of OCSs (hazard ratio HA 1.10; 95 confidence interval CI 1.07-1.18). ICS/LABA initiators were 62 less likely than ICS initiators (HR 0.38; 95 Cl 0.12-0.66) and 50 less likely than LABA initiators to receive OCS prescriptions for asthma exacerbations (HR 0.50; 95 CI 0.14-0.78). Conclusions: In concordance with current asthma management guidelines, inhaled LABAs should not be prescribed as monotherapy to patients with asthma. The findings suggest the presence of time dependent confounding by asthma severity, which was accounted for by the marginal structural model.