Macitentan in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease (CTD-PAH): Real-World Evidence from the Combined OPUS/OrPHeUS Dataset

• Published in: Cardiology and Therapy Vol. 13; no. 2; pp. 315 - 339
• Main Authors: Channick, Richard, Chin, Kelly M., McLaughlin, Vallerie V., Lammi, Matthew R., Zamanian, Roham T., Turricchia, Stefano, Ong, Rose, Mitchell, Lada, Kim, Nick H.
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.06.2024; Springer; Adis, Springer Healthcare
• Subjects: Cardiology; Care and treatment; Connective tissue disease; Internal Medicine; Macitentan; Medicine; Medicine & Public Health; Mixed connective tissue disease; NCT; NCT02126943; NCT03197688; Original Research; Patient outcomes; Pulmonary arterial hypertension; Pulmonary hypertension; Real-world evidence; Scleroderma; United States; Connective tissue disease; Macitentan; Systemic lupus erythematosus; Systemic sclerosis; Pulmonary arterial hypertension; Mixed connective tissue disease; Scleroderma; Real-world evidence
• ISSN: 2193-8261; 2193-6544
• DOI: 10.1007/s40119-024-00361-w

Introduction Data on real-world clinical practice and outcomes of patients with pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH) are scarce. The OPUS/OrPHeUS studies enrolled patients newly initiating macitentan, including those with CTD-PAH. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles of patients with CTD-PAH newly initiating macitentan in the US using the OPUS/OrPHeUS combined dataset. Methods OPUS was a prospective, US, multicenter, long-term, observational drug registry (April 2014–June 2020). OrPHeUS was a retrospective, US, multicenter medical chart review (October 2013–March 2017). The characteristics, treatment patterns, safety, and outcomes during macitentan treatment of patients with CTD-PAH and its subgroups systemic sclerosis (SSc-PAH), systemic lupus erythematosus (SLE-PAH), and mixed CTD (MCTD-PAH) were descriptively compared to patients with idiopathic/heritable PAH (I/HPAH). Results The combined OPUS/OrPHeUS population included 2498 patients with I/HPAH and 1192 patients with CTD-PAH (708 SSc-PAH; 159 SLE-PAH; 124 MCTD-PAH, and 201 other CTD-PAH etiologies). At macitentan initiation for patients with I/HPAH and CTD-PAH, respectively: 61.2 and 69.3% were in World Health Organization functional class (WHO FC) III/IV; median 6-min walk distance was 289 and 279 m; and 58.1 and 65.2% received macitentan as combination therapy. During follow-up, for patients with I/HPAH and CTD-PAH, respectively: median duration of macitentan exposure observed was 14.0 and 15.8 months; 79.0 and 83.0% experienced an adverse event; Kaplan–Meier estimates (95% confidence limits [CL]) of patients free from all-cause hospitalization at 1 year were 60.3% (58.1, 62.4) and 59.3% (56.1, 62.3); and Kaplan–Meier estimates (95% CL) of survival at 1 year were 90.5% (89.1, 91.7) and 90.6% (88.6, 92.3). Conclusions Macitentan was used in clinical practice in patients with CTD-PAH and its subgroups, including as combination therapy. The safety and tolerability profile of macitentan in patients with CTD-PAH was comparable to that of patients with I/HPAH. Trial Registration OPsumit® Users Registry (OPUS): NCT02126943; Opsumit® Historical Users cohort (OrPHeUS): NCT03197688; www.clinicaltrials.gov Graphical abstract available for this article. Graphical Abstract