(197) Using Real-World Data to Evaluate Comparative Effectiveness Cohorts of Azithromycin Relative to Roflumilast in Individuals with Uncontrolled Chronic Obstructive Pulmonary Disease

Publication Number: 1190

Background: Evidence from placebo-controlled trials indicate that chronic maintenance (CM) use of azithromycin (AZT) or roflumilast (ROF) may be beneficial in reducing morbidity associated with chronic obstructive pulmonary disease (COPD). However, comparative effectiveness evaluations are lacking. Randomized trials to address such questions are generally resource intensive.

Objectives: To describe and evaluate the feasibility of using a real-world data source to determine the effectiveness of CM AZT versus CM ROF in preventing COPD-related morbidity and all-cause mortality.

Methods: We conducted an active comparator, new user cohort study using administrative claims data from the Centers for Medicare and Medicaid Services. Our cohort included patients with COPD aged >= 40 years newly initiating CM therapy with AZT (evidence of supply >=14 days) or ROF between 3/1/2011 and 12/31/2018. The final cohort included patients with at least one study-defined moderate-to-severe COPD exacerbation (MSCE) in the year prior to initiation of CM AZT or ROF despite evidence of at least 183 days supplied of inhaled corticosteroid, long-acting beta-agonist, and long-acting muscarinic antagonist in the preceding year, and without evidence of comorbid respiratory conditions or other conditions treated with CM AZT. Follow-up began the day after cohort entry and ended at the earliest occurrence of MSCE, treatment cessation or crossover, disenrollment, death, or 1 year since cohort entry. New users of CM AZT and ROF were matched 1:1 on propensity scores to control for measured confounding. Balance was evaluated using absolute standardized mean differences (SMD) at a threshold of 0.10 to indicate meaningful differences.

Results: Prior to matching, we identified 1,375 new users of CM AZT and 3,435 new users of ROF. New users of AZT were older (mean AZT: 71.4 ± 8.7 years vs. ROF: 69.7 ± 8.8 years; absolute SMD 0.19) and were more likely to have the emphysematous phenotype of COPD (AZT: 46.5% vs. ROF: 35.9%; absolute SMD 0.22). New users of ROF were more likely to have the chronic bronchitis phenotype of COPD (AZT: 42.0% vs. ROF: 54.7%; SMD 0.26) and associated diagnoses including congestive heart failure and obstructive sleep apnea. After matching, there were 1,283 patients in each arm. Study arms were balanced on measured characteristics (SMD < 0.1) indicating robust control for measured confounding.

Conclusions: This study demonstrates that well-designed observational studies using real-world data can generate informative comparisons to guide investigations of comparative effectiveness. Our study created a well-defined target population among whom measures of effectiveness may be estimated with minimal confounding.