Real-World Characteristics, Treatment Patterns, and Clinical Outcomes of Patients Initiated on Macitentan/Tadalafil Single-Tablet Combination Therapy in the United States.

Abstract

Introduction: Pulmonary arterial hypertension (PAH) is life-threatening and often complicated by comorbidities. Although endothelin receptor antagonist (ERA) plus phosphodiesterase 5 inhibitor (PDE5i) dual therapy is guideline recommended, real-world treatment varies. Macitentan/tadalafil fixed-dose combination (M/T FDC) is a once-daily single-tablet dual therapy approved in March 2024. This study characterized patient characteristics, treatment patterns, and exploratory outcomes.

Methods: In this retrospective chart review, 50 US healthcare providers reviewed patient charts during structured interviews. Patients were categorized as ERA/PDE5i/soluble guanylate cyclase (sGC)-naïve, escalated from monotherapy, or switched from ERA plus PDE5i/sGC combination therapy. Outcomes included baseline characteristics, treatment patterns, reasons for M/T FDC initiation, 6-min walk distance (6MWD), brain natriuretic peptide (BNP), and PAH-related hospitalizations.

Results: Providers reviewed 144 charts; 83.3% of patients had at least one comorbidity. Overall, 51.4% switched from dual therapy, 28.5% escalated from monotherapy, and 20.1% were ERA/PDE5i/sGC-naïve. Naïve patients frequently had connective tissue disease-associated or drug- and toxin-induced PAH. Reduced pill burden was the leading reason for initiation. Among patients without concomitant prostacyclin or activin signaling inhibitor initiation or escalation and with paired baseline and follow-up data, mean favorable numerical changes were observed: 6MWD increased by 51.0 m (355.2-406.2; n = 36), BNP decreased by 167.8 pg/mL (357.0-189.2; n = 29), and PAH-related hospitalizations decreased from 0.18 to 0.05 events per patient (n = 65) over approximately 3 months.

Conclusion: M/T FDC is being adopted across diverse US PAH populations, including patients with comorbidities, most commonly to reduce pill burden and simplify treatment administration. Exploratory descriptive analyses showed favorable numerical changes in selected clinical parameters among patients with available paired data. However, because the study was retrospective, non-comparative, and not powered for hypothesis testing, these findings should be interpreted as hypothesis-generating. These results provide early insights into use of M/T FDC use and identify areas for future longitudinal and comparative research.