Effectiveness of Fixed Triple Combination Inhaled Corticosteroid (ICS), Long-Acting Beta-Agonist (LABA), and Long-Acting Muscarinic Antagonist (LAMA) Products vs. Multiple Inhaler ICS, LABA, LAMA Therapy in Patients With COPD

The Chronic Obstructive Pulmonary Disease (COPD), Asthma, and Respiratory Disease Effectiveness (CARE) study was opened in support of the FDA’s 21st Century Cures Act (Cures Act), signed into law on December 13, 2016. In this CARE project, we will compare the effectiveness of therapy with fixed triple combination (fixed) inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), and long-acting muscarinic antagonist (LAMA) products (Trelegy Ellipta, approved for COPD on September 18, 2017; and Breztri Aerosphere, approved on July 23, 2020) to administration of ICS, LABA, and LAMA components in multiple inhalers (e.g., fixed double combination ICS/LABA product plus separate LAMA product) in patients with COPD. This activity will use existing Sentinel tools and supplemental programming to compare outcomes of interest, which may include COPD exacerbations, hospitalizations, and surrogates of medication adherence. Importantly, results from this study are expected to provide some of the earliest and most robust data comparing triple combination single and multiple inhaler therapies for COPD.

In earlier CARE projects, we conducted extensive exploratory and descriptive analyses to define cohorts of COPD patients, identify patterns of COPD medication dispensing, and identify rates of COPD exacerbations. Subsequent analyses identified the baseline characteristics of cohorts of COPD patients treated with roflumilast and azithromycin, respectively, as well as as-treated and intent-to-treat analyses assessing the afore-mentioned outcomes. This initial work was then applied to explore the clinical effectiveness of azithromycin versus roflumilast among patients who continue to experience COPD exacerbations despite triple inhaled therapy using observational data from the Sentinel Distributed Database (SDD). This trial emulation explores a question similar to the RELIANCE randomized trial, an ongoing, parallel, pragmatic, non-inferiority trial comparing the efficacy of roflumilast versus azithromycin in preventing hospitalization or death among patients at high risk of COPD exacerbations. This analysis of fixed combination triple vs. multiple inhaler therapy effectiveness will similarly draw from the initial work to inform cohort, exposure, and outcome definitions.

A draft protocol will be made available for public comment.