Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies

Overview

Journal Pulm Ther

Publisher Springer

Date 2024 Jan 6

PMID 38184507

Authors

Nick H Kim

Kelly M Chin

Vallerie V McLaughlin

Hilary Dubrock

Ricardo Restrepo-Jaramillo

Zeenat Safdar

Gwen MacDonald

Nicolas Martin

Daniel Rosenberg

Maria Solonets

Richard Channick

Affiliations

Soon will be listed here.

Abstract

Introduction: Portopulmonary hypertension (PoPH) carries a worse prognosis than other forms of pulmonary arterial hypertension (PAH). Data regarding use of PAH-specific therapies in patients with PoPH are sparse as they are usually excluded from clinical trials. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles in patients with PoPH newly initiating macitentan in the USA using the OPUS/OrPHeUS combined dataset.

Methods: OPUS was a prospective, US, multicenter, observational drug registry (April 2014-June 2020); OrPHeUS was a retrospective, US, multicenter chart review (October 2013-March 2017). Additional information regarding patients' liver disease was retrospectively collected for patients with PoPH in OPUS.

Results: The OPUS/OrPHeUS dataset included 206 patients with PoPH (median age 58 years; 52.4% female), with baseline cirrhosis and liver test abnormalities reported in 72.8% and 31.6% of patients respectively. Macitentan was initiated as combination therapy in 74.8% of patients and median (Q1, Q3) exposure to macitentan was 11.9 (3.1, 26.0) months. One-year Kaplan-Meier estimates (95% confidence limit, CL) of patients free from all-cause hospitalization and survival were 48.6% (40.7, 56.0) and 82.2% (75.1, 87.4). Of the 96 patients with PoPH in OPUS, 29.2% were classified as in need of liver transplant due to underlying liver disease during the study; transplant waitlist registration was precluded because of PAH severity for 32.1% and 17.9% were transplanted. Hepatic adverse events (HAE) were experienced by 49.0% of patients; the most common being increased bilirubin (16.0%), ascites (7.3%), and hepatic encephalopathy (5.8%); 1.5% and 21.8% of patients discontinued macitentan as a result of HAE and non-hepatic adverse events.

Conclusion: There were no unexpected safety findings in patients with PoPH treated with macitentan. These data add to the evidence supporting the safety and tolerability of macitentan in patients with PoPH. A graphical abstract is available with this article.

Trial Registration: OPsumit® Users Registry (OPUS): NCT02126943; OPsumit® Historical Users cohort (OrPHeUS): NCT03197688; www.

Clinicaltrials: gov .

Citing Articles

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

Chin K, Channick R, Kim N, Ong R, Turricchia S, Martin N Cardiol Ther. 2024; 13(4):775-796.

PMID: 39585521 PMC: 11607228. DOI: 10.1007/s40119-024-00386-1.

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