Author information
1UC San Diego Health, Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037-7381, USA. h33kim@ucsd.edu.
2UT Southwestern Medical Center, Dallas, TX, USA.
3University of Michigan, Ann Arbor, MI, USA.
4Mayo Clinic, Rochester, MN, USA.
5University of South Florida, Tampa, FL, USA.
6Houston Methodist, Weill Cornell Medical College, Houston, TX, USA.
7Global Medical Affairs, Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and Johnson, Allschwil, Switzerland.
8Statistical Decision Science, Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and Johnson, Allschwil, Switzerland.
9Global Epidemiology, Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and Johnson, Allschwil, Switzerland.
10Global Medical Safety, Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and Johnson, Allschwil, Switzerland.
11David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
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 .