Evaluating Triple Therapy Treatment Pathways in Chronic Obstructive Pulmonary Disease (COPD): A Machine-Learning Predictive Model

PURPOSE: Inhaled triple therapy (TT) comprising a long-acting muscarinic antagonist, long-acting β(2) agonist, and inhaled corticosteroid is recommended for symptomatic chronic obstructive pulmonary disease (COPD) patients, or those at risk of exacerbation. However, it is not well understood which patient characteristics contribute most to future exacerbation risk. This study assessed patient predictors associated with future exacerbation time following initiation of TT. PATIENTS AND METHODS: This retrospective cohort study used data from the Optum™ Clinformatics™ Data Mart, a large health claims database in the United States. COPD patients who initiated TT between January 2008 and March 2018 (index) were eligible. Patients were required to be aged ≥18 years at index and have continuous enrollment for the 12 months prior to index (baseline) and the 12 months following index (follow-up). Patients who had received TT during baseline were excluded. Data from eligible patients were analyzed using a reverse engineering forward simulation machine learning platform to predict future COPD exacerbation time. RESULTS: Data from 73,625 patients were included. The model found that prior exacerbation was largely correlated with post-index exacerbation time; patients who had ≥4 exacerbation episodes during baseline had an average increase of 32.4 days post-index exacerbation, compared with patients with no exacerbations during baseline. Likewise, ≥2 inpatient visits (effect size 27.1 days), the use of xanthines (effect size 11.5 days), or rheumatoid arthritis (effect size 6.4 days) during baseline were associated with increased exacerbation time. Conversely, diagnosis of anemia (effect size –5.68 days), or oral corticosteroids in the past month (effect size –3.43 days) were associated with reduced exacerbation time. CONCLUSION: Frequent prior exacerbations, healthcare resource utilization, xanthine use, and rheumatoid arthritis were the strongest factors predicting the future increase of exacerbations. These results improve our understanding of exacerbation risk among COPD patients initiating triple therapy.