Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies
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 patie...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2024-01-01
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| Series: | Pulmonary Therapy |
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| Online Access: | https://doi.org/10.1007/s41030-023-00251-x |
| _version_ | 1827326607191179264 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nick H. Kim |
| collection | DOAJ |
| description | 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 . Graphical Abstract |
| first_indexed | 2024-03-07T14:48:03Z |
| format | Article |
| id | doaj.art-d2d527f021da4bc98cd27bae7d4bdc4e |
| institution | Directory Open Access Journal |
| issn | 2364-1754 2364-1746 |
| language | English |
| last_indexed | 2024-03-07T14:48:03Z |
| publishDate | 2024-01-01 |
| publisher | Adis, Springer Healthcare |
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| series | Pulmonary Therapy |
| spelling | doaj.art-d2d527f021da4bc98cd27bae7d4bdc4e2024-03-05T19:52:38ZengAdis, Springer HealthcarePulmonary Therapy2364-17542364-17462024-01-011018510710.1007/s41030-023-00251-xSafety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS StudiesNick H. Kim0Kelly M. Chin1Vallerie V. McLaughlin2Hilary DuBrock3Ricardo Restrepo-Jaramillo4Zeenat Safdar5Gwen MacDonald6Nicolas Martin7Daniel Rosenberg8Maria Solonets9Richard Channick10UC San Diego Health, Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San DiegoUT Southwestern Medical CenterUniversity of MichiganMayo ClinicUniversity of South FloridaHouston Methodist, Weill Cornell Medical CollegeGlobal Medical Affairs, Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and JohnsonStatistical Decision Science, Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and JohnsonGlobal Epidemiology, Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and JohnsonGlobal Medical Safety, Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson and JohnsonDavid Geffen School of Medicine, University of California Los AngelesAbstract 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 Abstracthttps://doi.org/10.1007/s41030-023-00251-xMacitentanPortopulmonary hypertensionPulmonary arterial hypertensionReal-world evidence |
| spellingShingle | 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 Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies Pulmonary Therapy Macitentan Portopulmonary hypertension Pulmonary arterial hypertension Real-world evidence |
| title | Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies |
| title_full | Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies |
| title_fullStr | Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies |
| title_full_unstemmed | Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies |
| title_short | Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies |
| title_sort | safety of macitentan for the treatment of portopulmonary hypertension real world evidence from the combined opus orpheus studies |
| topic | Macitentan Portopulmonary hypertension Pulmonary arterial hypertension Real-world evidence |
| url | https://doi.org/10.1007/s41030-023-00251-x |
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