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      Comparative Treatment Persistence and Adherence to Endothelin Receptor Antagonists Among Patients with Pulmonary Arterial Hypertension in Japan: A Real-World Administrative Claims Database Study

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          Abstract

          Introduction

          Real-world data on the comparative effectiveness of endothelin receptor antagonists (ERAs; macitentan, bosentan, ambrisentan) for pulmonary arterial hypertension (PAH), particularly in Asian countries, are scarce. We evaluated the persistence of these ERAs before and after macitentan approval in Japan (2015).

          Methods

          We used real-world data from the Japanese Medical Data Vision administrative claims database between April 2008 and November 2020. Patients with PAH were identified from the dataset. Persistence to ERA treatment before and after approval of macitentan in Japan was defined as the time between start of the index ERA and treatment discontinuation or death. Propensity score adjustment was applied to minimize confounding effects among treatment groups.

          Results

          In the pre-macitentan approval cohort, 153 and 51 patients received bosentan and ambrisentan, respectively. In the post-macitentan approval cohort, 331, 284, and 91 patients received macitentan, bosentan, and ambrisentan, respectively. Unadjusted median persistence for ambrisentan- and bosentan-treated patients was 19 and 10 months, respectively (adjusted HR 0.87 [95% CI 0.61–1.24]; P = 0.434 [bosentan as reference]). In the post-macitentan approval cohort, unadjusted median persistence was 18 months for macitentan-treated patients versus 6 and 8 months for ambrisentan- and bosentan-treated patients, respectively. Adjusted HRs for ambrisentan and bosentan were 1.48 (95% CI 1.12–1.95; P = 0.006) and 1.63 (95% CI 1.30–2.04; P < 0.001 [macitentan as reference]), respectively.

          Conclusions

          Real-world data for Japanese patients with PAH showed that persistence was significantly higher for macitentan, versus ambrisentan and bosentan, since its approval.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s41030-023-00244-w.

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          Most cited references35

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          2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).

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            Risk stratification and medical therapy of pulmonary arterial hypertension

            Pulmonary arterial hypertension (PAH) remains a severe clinical condition despite the availability over the past 15 years of multiple drugs interfering with the endothelin, nitric oxide and prostacyclin pathways. The recent progress observed in medical therapy of PAH is not, therefore, related to the discovery of new pathways, but to the development of new strategies for combination therapy and on escalation of treatments based on systematic assessment of clinical response. The current treatment strategy is based on the severity of the newly diagnosed PAH patient as assessed by a multiparametric risk stratification approach. Clinical, exercise, right ventricular function and haemodynamic parameters are combined to define a low-, intermediate- or high-risk status according to the expected 1-year mortality. The current treatment algorithm provides the most appropriate initial strategy, including monotherapy, or double or triple combination therapy. Further treatment escalation is required in case low-risk status is not achieved in planned follow-up assessments. Lung transplantation may be required in most advanced cases on maximal medical therapy.
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              Pulmonary arterial hypertension in France: results from a national registry.

              Pulmonary arterial hypertension (PAH) is an orphan disease for which the trend is for management in designated centers with multidisciplinary teams working in a shared-care approach. To describe clinical and hemodynamic parameters and to provide estimates for the prevalence of patients diagnosed for PAH according to a standardized definition. The registry was initiated in 17 university hospitals following at least five newly diagnosed patients per year. All consecutive adult (> or = 18 yr) patients seen between October 2002 and October 2003 were to be included. A total of 674 patients (mean +/- SD age, 50 +/- 15 yr; range, 18-85 yr) were entered in the registry. Idiopathic, familial, anorexigen, connective tissue diseases, congenital heart diseases, portal hypertension, and HIV-associated PAH accounted for 39.2, 3.9, 9.5, 15.3, 11.3, 10.4, and 6.2% of the population, respectively. At diagnosis, 75% of patients were in New York Heart Association functional class III or IV. Six-minute walk test was 329 +/- 109 m. Mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance index were 55 +/- 15 mm Hg, 2.5 +/- 0.8 L/min/m(2), and 20.5 +/- 10.2 mm Hg/L/min/m(2), respectively. The low estimates of prevalence and incidence of PAH in France were 15.0 cases/million of adult inhabitants and 2.4 cases/million of adult inhabitants/yr. One-year survival was 88% in the incident cohort. This contemporary registry highlights current practice and shows that PAH is detected late in the course of the disease, with a majority of patients displaying severe functional and hemodynamic compromise.
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                Author and article information

                Contributors
                ymakanji@its.jnj.com
                Journal
                Pulm Ther
                Pulm Ther
                Pulmonary Therapy
                Springer Healthcare (Cheshire )
                2364-1754
                2364-1746
                22 November 2023
                22 November 2023
                December 2023
                : 9
                : 4
                : 511-526
                Affiliations
                [1 ]GRID grid.519059.1, Janssen Pharmaceuticals, ; Tokyo, Japan
                [2 ]Janssen Pharmaceutical Asia Pacific, 2 Science Park Dr, #07-13, Singapore, 118882 Singapore
                [3 ]Pulmonary Hypertension Center, Chibaken Saiseikai Narshino Hospital, ( https://ror.org/00259c050) Chiba, Japan
                [4 ]Prospection KK, Tokyo, Japan
                [5 ]Prospection, Haymarket, NSW Australia
                Article
                244
                10.1007/s41030-023-00244-w
                10721767
                37991630
                4ab48229-4117-466b-bcf7-c69f35a10c81
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 30 August 2023
                : 6 November 2023
                Funding
                Funded by: Janssen Asia Pacific Medical Affairs
                Categories
                Original Research
                Custom metadata
                © Springer Healthcare Ltd., part of Springer Nature 2023

                endothelin receptor antagonists,japanese patients,pulmonary arterial hypertension,real-world data,treatment persistence

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