Macitentan in Pulmonary Arterial Hypertension Due to Congenital Heart Disease (CHD-PAH): Real-World Evidence from the OPUS/OrPHeUS Studies.

Introduction: Data on real-world clinical practice and outcomes of patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) are scarce. The OPUS/OrPHeUS studies enrolled patients with PAH newly initiating macitentan, including those with PAH associated with CHD (CHD-PAH).
Methods: OPUS was a prospective, United States, multicenter, long-term, observational drug registry (April 2014-June 2020). OrPHeUS was a retrospective, United States, multicenter medical chart review (October 2013-March 2017). The characteristics, treatment patterns, safety, and outcomes during macitentan treatment of patients with CHD-PAH and the subgroups Eisenmenger syndrome, left-to-right shunts and small/coincidental CHD were descriptively compared.
Results: The combined OPUS/OrPHeUS population included 272 (6.1%) patients with CHD-PAH (80 patients with Eisenmenger syndrome; 82 patients with left-to-right shunts and 92 patients with small/coincidental defects). Most patients across the CHD-PAH subgroups were in World Health Organization Functional Class II/III (82.9-94.6%). Macitentan was initiated as combination therapy in 65.0% of patients with CHD-PAH. During follow-up, 81.4% of patients experienced ≥ 1 adverse event (AE), the most common being dyspnea (23.5%), nausea (13.7%), dizziness (12.7%), headache (12.7%) and edema (10.8%). The 1- and 2-year Kaplan-Meier (95% confidence limits) estimates of patients with CHD-PAH being free from hospitalization were 64.5% (57.9, 70.4) and 49.3% (41.9, 56.3); for survival, the 1- and 2-year Kaplan-Meier estimates were 93.5% (89.3, 96.1) and 90.2% (84.9, 93.7).
Conclusions: Macitentan was used in clinical practice in patients with CHD-PAH and its subgroups, including as combination therapy in the majority of patients. Safety in this population was consistent with the known profile of macitentan.
Trial Registration: OPsumit ^® Users Registry (OPUS): NCT02126943; Opsumit ^® Historical Users cohort (OrPHeUS): NCT03197688; URL www.
Clinicaltrials: gov .
Competing Interests: Declarations. Conflict of Interest: Kelly M Chin has served as a Scientific Committee member for Johnson & Johnson; has received research grants/support from Johnson & Johnson, Altavant, Acceleron, United Therapeutics, Pfizer, Merck, Gossamer Bio; has received support for travel to meetings from Johnson & Johnson; and has received consultancy fees from Johnson & Johnson, Altavant, Acceleron, United Therapeutics and Gossamer Bio. Richard Channick served as a Scientific Committee member for Johnson & Johnson; served on an advisory board for Johnson & Johnson and Bayer; received research grants/support from Johnson & Johnson and United therapeutics; received speaker fees from Johnson & Johnson, and Bayer; received consultancy fees from Johnson & Johnson, Bayer and Third pole. Nick H Kim served as a Scientific Committee member for Johnson & Johnson; received research grants/support from Enzyvant and Lung Biotechnology; received consultant fees from Johnson & Johnson, Bayer, Merck, United Therapeutics, Gossamer Bio, Pulnovo and Polarean; and received speaker fees from Johnson & Johnson, Bayer and Merck. Rose Ong is an employee of Johnson & Johnson; has received support for travel to meetings from Johnson & Johnson; holds stock or stock options with Johnson & Johnson; and spouse is an employee of Roche. Stefano Turricchia, Nicolas Martin and Lada Mitchell are employees of Johnson & Johnson. Vallerie V McLaughlin served as a Scientific Committee member from Johnson & Johnson; received research grants from Aerovate, Altavant, Gossamer Bio, Johnson & Johnson, Merck, and SoniVie; and received consultant fees from Aerami, Aerovate, Altavant, Bayer, Caremark, Corvista, Gossamer Bio, Johnson & Johnson, L.L.C, Merck and United Therapeutics. Ethical Approval: OPUS and OrPHeUS were executed in accordance with Good Pharmacoepidemiology Practices [29] and the 2008 Declaration of Helsinki ethical principles. Ethical approval was obtained from independent ethics committees/institutional review boards (IRB) of participating centers (see Supplementary Methods 1 for a full site list including local ethical review boards) and overseen by an Independent Scientific Committee (Supplementary Methods 2) with protocols reviewed by the US FDA. IRB approvals were provided by the Western IRB and Quorum (now Advarra) (OPUS registry; Western IRB approval number 2014‐0816, Quorum Review File number 29120/Advarra Pro00035124) and WCG‐IRB (OrPHeUS study; IRB numbers 2017‐8051 and 2017‐2348). In OPUS, written informed consent was obtained from all patients, including for publication of anonymized patient data (in OrPHeUS, an IRB waiver for informed consent was obtained). The informed consent form in OPUS included a confidentiality clause that all records and documents pertaining to the participation of patients in the OPUS registry would be held strictly confidential and their names would not be reported in any publications resulting from the OPUS registry. Following the approval of macitentan by the US FDA for the long-term treatment of PAH, OPUS and OrPHeUS were initiated as a post-marketing requirement to evaluate the potential risks for liver toxicity with macitentan use. This post-marketing requirement was completed in September 2019.
(© 2024. The Author(s).)