Real-world use of initial combination treatment in the management of pulmonary arterial hypertension

Background: Initial regimen selection is critical for pulmonary arterial hypertension (PAH) management and survival. Since 2015, guidelines have recommended upfront combination therapy as the standard of care in newly diagnosed patients. Objectives: To highlight real-world treatment patterns and predictors of initial combination therapy. Design: Retrospective cohort analysis of U.S. administrative claims from 01 January 2013 (Optum’s de-identified Clinformatics^®Data Mart Database [CDM]) or 01 July/2015 (IQVIA PharMetrics^®Plus) through 30 September 2020. Methods: Patients initiating PAH medications (phosphodiesterase-5 inhibitors (PDE5i), soluble guanylate cyclase stimulators (SGCS), endothelin receptor antagonists (ERA), or prostacyclin analogues (PCY)) were identified and indexed on the first medication date. All PAH medications identified between index and 365 days post-index were identified and classified as PDE5i/SGCS/ERA monotherapy, PDE5i/SGCS + ERA dual therapy, or PCY-containing regimen. Treatment regimens were analyzed by index year, physician specialty, and among physician specialists associated with a Pulmonary Hypertension Care Center. Multivariable regression was conducted to identify patient characteristics predictive of the first-line regimen. Results: 1754 (CDM) and 1107 (IQVIA PharMetrics Plus) met selection criteria. The most initiated first-line regimen was PDE5i/SGCS/ERA monotherapy (CDM: 61.2%; IQVIA PharMetrics Plus: 50.9%). The proportion of CDM patients initiating PDE5i/SGCS + ERA dual therapy increased from 13.1% in 2013 to 21.9% in 2019; for IQVIA PharMetrics Plus, PDE5i/SGCS + ERA dual therapy remained consistent (24.4% in 2015, 23.7% in 2019). More pulmonologists prescribed PDE5i/SGCS + ERA dual therapy (CDM: 30.2%; IQVIA PharMetrics Plus: 38.6%) than cardiologists (CDM: 18.3%; IQVIA PharMetrics Plus: 24.3%). PHCC patients were prescribed first-line dual therapy (35.7% vs 26.9%) and PCY-containing regimens (30.3% vs 21.7%) more frequently than non-PHCC patients, respectively. Females (vs males) were more likely to receive dual therapy and PCY-containing regimens; Black (vs White) patients were less likely to receive PCY-containing regimens. Conclusion: Additional research is needed to better understand barriers to optimal initial treatment regimen selection and to quantify the impacts of therapeutic delay.