TY - JOUR
T1 - Safety of macitentan for the treatment of pulmonary hypertension
T2 - Real-world experience from the OPsumit® USers Registry (OPUS) and OPsumit® Historical USers cohort (OrPHeUS)
AU - McLaughlin, Vallerie V.
AU - Channick, Richard
AU - Kim, Nick H.
AU - Frantz, Robert P.
AU - McConnell, John W.
AU - Melendres-Groves, Lana
AU - Miller, Chad
AU - Ravichandran, Ashwin
AU - Rodriguez-Lopez, Josanna
AU - Brand, Monika
AU - Leroy, Sandrine
AU - Wetherill, Graham
AU - Chin, Kelly M.
N1 - Funding Information:
The OPUS Registry and the OrPHeUS medical chart review were sponsored by Actelion Pharmaceuticals Ltd., a Janssen Pharmaceutical Company of Johnson & Johnson. The Sponsor participated in the conception and design of the analysis and interpretation of the data, drafting and critical revision of the report, and approved submission of the manuscript. Medical writing assistance was provided by Caroline Wadsworth (eluSCIdate Ltd., Meggen, Switzerland) and was funded by Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson. Clinical evaluation of hepatic safety was performed by the ILSDRB: Willis Maddrey MD (chairperson), Paul Watkins, MD, and James Freston, MD. Megan Flynn, PhD contributed to the analysis of data and development of the manuscript. OPUS and OrPHeUS were funded by Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson.
Funding Information:
This work was supported by Career Development Award Number IK2 RX003282 and Merit Review Number I01 RX003699 from the United States Department of Veterans Affairs Rehabilitation R&D Service.
Publisher Copyright:
© 2022 Actelion Pharmaceuticals Ltd. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.
PY - 2022/10
Y1 - 2022/10
N2 - Macitentan is an oral endothelin receptor antagonist for the management of pulmonary arterial hypertension (PAH). The OPsumit® USers Registry (OPUS) and the OPsumit® Historical USers cohort (OrPHeUS) medical chart review provide real-world data for patients newly initiating macitentan. This study aims to describe the characteristics, safety profile, and clinical outcomes of PAH patients newly treated with macitentan in the combined OPUS/OrPHeUS data set. OPUS was a prospective, multicenter, long-term, observational drug registry from April 2014 to June 2020. OrPHeUS was a retrospective, US, multicenter chart review: observation period October 2013 to March 2017. All analyses were descriptive. At registry closure in June 2020, the combined population consisted of 5654 patients, of whom 81.9% were diagnosed with PAH. For these 4626 patients, median duration of macitentan exposure observed was 14.5 (Q1 = 5.2, Q3 = 29.0) months; idiopathic PAH (54.8%) was the most common form of PAH; macitentan was initiated as monotherapy (37.9%), or as part of double (48.0%) or triple therapy (14.1%); discontinuation due to nonhepatic/hepatic adverse events occurred in 17.1%/0.3% of patients; 9.9% of patients experienced ≥1 hepatic adverse events; Kaplan–Meier estimates showed that at 1 year 59.9% (95% confidence interval: 58.3, 61.5) of patients were free from hospitalization and survival was 90.4% (89.3, 91.3). This analysis of real-world data from the combined OPUS and OrPHeUS populations demonstrated that macitentan is well tolerated in a large, diverse population of PAH patients, with overall and hepatic safety profiles consistent with previous macitentan clinical trials.
AB - Macitentan is an oral endothelin receptor antagonist for the management of pulmonary arterial hypertension (PAH). The OPsumit® USers Registry (OPUS) and the OPsumit® Historical USers cohort (OrPHeUS) medical chart review provide real-world data for patients newly initiating macitentan. This study aims to describe the characteristics, safety profile, and clinical outcomes of PAH patients newly treated with macitentan in the combined OPUS/OrPHeUS data set. OPUS was a prospective, multicenter, long-term, observational drug registry from April 2014 to June 2020. OrPHeUS was a retrospective, US, multicenter chart review: observation period October 2013 to March 2017. All analyses were descriptive. At registry closure in June 2020, the combined population consisted of 5654 patients, of whom 81.9% were diagnosed with PAH. For these 4626 patients, median duration of macitentan exposure observed was 14.5 (Q1 = 5.2, Q3 = 29.0) months; idiopathic PAH (54.8%) was the most common form of PAH; macitentan was initiated as monotherapy (37.9%), or as part of double (48.0%) or triple therapy (14.1%); discontinuation due to nonhepatic/hepatic adverse events occurred in 17.1%/0.3% of patients; 9.9% of patients experienced ≥1 hepatic adverse events; Kaplan–Meier estimates showed that at 1 year 59.9% (95% confidence interval: 58.3, 61.5) of patients were free from hospitalization and survival was 90.4% (89.3, 91.3). This analysis of real-world data from the combined OPUS and OrPHeUS populations demonstrated that macitentan is well tolerated in a large, diverse population of PAH patients, with overall and hepatic safety profiles consistent with previous macitentan clinical trials.
KW - cardiopulmonary disease
KW - epidemiology
KW - hepatic safety
KW - pulmonary arterial hypertension
KW - real-world evidence
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U2 - 10.1002/pul2.12150
DO - 10.1002/pul2.12150
M3 - Article
C2 - 36381290
AN - SCOPUS:85145041538
SN - 2045-8932
VL - 12
JO - Pulmonary Circulation
JF - Pulmonary Circulation
IS - 4
M1 - e12150
ER -