TY - JOUR
T1 - Safety of Macitentan for the Treatment of Portopulmonary Hypertension
T2 - Real-World Evidence from the Combined OPUS/OrPHeUS Studies
AU - Kim, Nick H.
AU - Chin, Kelly M.
AU - McLaughlin, Vallerie V.
AU - DuBrock, Hilary
AU - Restrepo-Jaramillo, Ricardo
AU - Safdar, Zeenat
AU - MacDonald, Gwen
AU - Martin, Nicolas
AU - Rosenberg, Daniel
AU - Solonets, Maria
AU - Channick, Richard
N1 - Publisher Copyright:
© The Author(s) 2024. corrected publication 2024.
PY - 2024/3
Y1 - 2024/3
N2 - 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. Graphical Abstract: (Figure presented.).
AB - 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. Graphical Abstract: (Figure presented.).
KW - Macitentan
KW - Portopulmonary hypertension
KW - Pulmonary arterial hypertension
KW - Real-world evidence
UR - http://www.scopus.com/inward/record.url?scp=85181492321&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85181492321&partnerID=8YFLogxK
U2 - 10.1007/s41030-023-00251-x
DO - 10.1007/s41030-023-00251-x
M3 - Article
C2 - 38184507
AN - SCOPUS:85181492321
SN - 2364-1754
VL - 10
SP - 85
EP - 107
JO - Pulmonary Therapy
JF - Pulmonary Therapy
IS - 1
ER -