{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:01:09Z","timestamp":1791489669706,"version":"4.3.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson & Johnson","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1007\/s12325-026-03525-3","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:35:02Z","timestamp":1773336902000},"page":"2106-2124","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-Term Treatment with Single-Tablet Combination of Macitentan and Tadalafil in Pulmonary Arterial Hypertension: Results from A DUE and Its Open-Label Period"],"prefix":"10.1007","volume":"43","author":[{"given":"H. James","family":"Ford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenling","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Friberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Gr\u00fcnig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob A.","family":"Hauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Pannaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany","family":"Rofael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3711-7064","authenticated-orcid":false,"given":"Pavel","family":"Jansa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"3525_CR1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01325-2024","volume":"64","author":"Km Chin","year":"2024","unstructured":"Chin KM, Gaine SP, Gerges C, Jing Z-C, Mathai SC, Tamura Y, et al. Treatment algorithm for pulmonary arterial hypertension. Eur Respir J. 2024;64:2401325. https:\/\/doi.org\/10.1183\/13993003.01325-2024.","journal-title":"Eur Respir J"},{"key":"3525_CR2","doi-asserted-by":"publisher","first-page":"3618","DOI":"10.1093\/Eurheartj\/Ehac237","volume":"43","author":"M Humbert","year":"2022","unstructured":"Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger R, Brida M, et al. 2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43:3618\u2013731. https:\/\/doi.org\/10.1093\/Eurheartj\/Ehac237.","journal-title":"Eur Heart J"},{"key":"3525_CR3","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00879-2022","volume":"61","author":"M Humbert","year":"2023","unstructured":"Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger R, Brida M, et al. 2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2023;61:2200879. https:\/\/doi.org\/10.1183\/13993003.00879-2022.","journal-title":"Eur Respir J"},{"key":"3525_CR4","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1056\/Nejmoa1413687","volume":"373","author":"N Gali\u00e8","year":"2015","unstructured":"Gali\u00e8 N, Barber\u00e0 JA, Frost AE, Ghofrani HA, Hoeper MM, Mclaughlin VV, et al. Initial use of Ambrisentan plus Tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373:834\u201344. https:\/\/doi.org\/10.1056\/Nejmoa1413687.","journal-title":"N Engl J Med"},{"key":"3525_CR5","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1183\/13993003.02043-2015","volume":"47","author":"O Sitbon","year":"2016","unstructured":"Sitbon O, Sattler C, Bertoletti L, Savale L, Cottin V, Jais X, et al. Initial dual oral combination therapy in pulmonary arterial hypertension. Eur Respir J. 2016;47:1727\u201336. https:\/\/doi.org\/10.1183\/13993003.02043-2015.","journal-title":"Eur Respir J"},{"key":"3525_CR6","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1183\/16000617.0085-2016","volume":"25","author":"O Sitbon","year":"2016","unstructured":"Sitbon O, Gaine S. Beyond a single pathway: combination therapy in pulmonary arterial hypertension. Eur Respir Rev. 2016;25:408\u201317. https:\/\/doi.org\/10.1183\/16000617.0085-2016.","journal-title":"Eur Respir Rev"},{"key":"3525_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/S40256-017-0260-1","volume":"18","author":"P Jansa","year":"2018","unstructured":"Jansa P, Pulido T. Macitentan in pulmonary arterial hypertension: a focus on combination therapy in the Seraphin trial. Am J Cardiovasc Drugs. 2018;18:1\u201311. https:\/\/doi.org\/10.1007\/S40256-017-0260-1.","journal-title":"Am J Cardiovasc Drugs"},{"key":"3525_CR8","doi-asserted-by":"publisher","first-page":"2000673","DOI":"10.1183\/13993003.00673-2020","volume":"56","author":"O Sitbon","year":"2020","unstructured":"Sitbon O, Canuet M, Picard C, Pr\u00e9vot G, Bergot E, Cottin V, et al. Initial combination therapy with macitentan and tadalafil in newly diagnosed patients with pulmonary arterial hypertension: results from the optima trial. Eur Respir J. 2020;56:2000673. https:\/\/doi.org\/10.1183\/13993003.00673-2020.","journal-title":"Eur Respir J"},{"key":"3525_CR9","doi-asserted-by":"publisher","unstructured":"Su\u00e1rez JA, Manzaneque A, Garcia NC, Creus MT, Mir JB. Risk of drug\u2013drug interactions in a pulmonary arterial hypertension population. Eur J Hosp Pharm. 2017;24:Di-058. https:\/\/doi.org\/10.1136\/Ejhpharm-2017-000640.305.","DOI":"10.1136\/Ejhpharm-2017-000640.305"},{"key":"3525_CR10","doi-asserted-by":"publisher","unstructured":"Ibrahim E. Concomitant medication use in treatment journey of pulmonary arterial hypertension patient: a canadian retrospective claims analysis. Am J Respir Criti Care Med. 2022:A5636. https:\/\/doi.org\/10.1164\/Ajrccm-Conference.2022.205.1_Meetingabstracts.A5636.","DOI":"10.1164\/Ajrccm-Conference.2022.205.1_Meetingabstracts.A5636"},{"key":"3525_CR11","doi-asserted-by":"publisher","DOI":"10.1007\/S40615-025-02579-3","author":"F Hw","year":"2025","unstructured":"Farber HW, Chakinala MM, Hemnes AR, Chin KM, Highland KB, McLaughlin VV, et al. Characteristics of patients with pulmonary arterial hypertension receiving selexipag in the SPHERE registry by race and ethnicity. J Racial Ethn Health Disparities 2025. https:\/\/doi.org\/10.1007\/S40615-025-02579-3.","journal-title":"J Racial Ethn Health Disparities"},{"key":"3525_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/Pul2.12326","volume":"14","author":"Hw Farber","year":"2024","unstructured":"Farber HW, Germack HD, Croteau NS, Simeone JC, Tang F, Paoli CJ, et al. Factors associated with discontinuation of treatment for pulmonary arterial hypertension in the United States. Pulm Circ. 2024;14:E12326. https:\/\/doi.org\/10.1002\/Pul2.12326.","journal-title":"Pulm Circ"},{"key":"3525_CR13","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01180-2024","author":"Ir Preston","year":"2024","unstructured":"Preston IR, Howard LS, Langleben D, Lichtblau M, Pulido T, Souza R, et al. Management of pulmonary hypertension in special conditions. Eur Respir J. 2024. https:\/\/doi.org\/10.1183\/13993003.01180-2024.","journal-title":"Eur Respir J"},{"key":"3525_CR14","doi-asserted-by":"publisher","first-page":"2298","DOI":"10.1007\/S12325-025-03159-X","volume":"42","author":"F Fan","year":"2025","unstructured":"Fan F, Davis S, Burbridge C, Chin K, Friberg M, Gr\u00fcnig E, et al. Single-tablet combination therapy of macitentan\/tadalafil for patients with pulmonary arterial hypertension: qualitative interview study of the A DUE phase 3 trial. Adv Ther. 2025;42:2298\u2013313. https:\/\/doi.org\/10.1007\/S12325-025-03159-X.","journal-title":"Adv Ther"},{"key":"3525_CR15","doi-asserted-by":"publisher","first-page":"115","DOI":"10.2147\/Ppa.S10330","volume":"4","author":"M Airoldi","year":"2010","unstructured":"Airoldi M, Zaccarelli M, Bisi L, Bini T, Antinori A, Mussini C, et al. One-pill once-a-day HAART: a simplification strategy that improves adherence and quality of life of HIV-infected subjects. Patient Prefer Adherence. 2010;4:115\u201325. https:\/\/doi.org\/10.2147\/Ppa.S10330.","journal-title":"Patient Prefer Adherence"},{"key":"3525_CR16","doi-asserted-by":"publisher","first-page":"8","DOI":"10.36469\/jheor.2024.91396","volume":"11","author":"Cj Paoli","year":"2024","unstructured":"Paoli CJ, Linder J, Gurjar K, Thakur D, Wyckmans J, Grieve S. Effectiveness of single-tablet combination therapy in improving adherence and persistence and the relation to clinical and economic outcomes. JHEOR. 2024;11:8\u201322.","journal-title":"Jheor"},{"key":"3525_CR17","doi-asserted-by":"publisher","DOI":"10.1002\/Pul2.70113","volume":"15","author":"Na Kolaitis","year":"2025","unstructured":"Kolaitis NA, Kingman M, Wilson M, Rendon GG, Lopez D, Paoli CJ, et al. Exploring providers\u2019 behaviors, attitudes, and preferences on the treatment of pulmonary arterial hypertension with endothelin receptor antagonist (Era) + phosphodiesterase-5 inhibitors (Pde5i). Pulm Circ. 2025;15:E70113. https:\/\/doi.org\/10.1002\/Pul2.70113.","journal-title":"Pulm Circ"},{"key":"3525_CR18","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/J.Jacc.2023.10.045","volume":"83","author":"E Gr\u00fcnig","year":"2024","unstructured":"Gr\u00fcnig E, Jansa P, Fan F, Hauser JA, Pannaux M, Morganti A, et al. Randomized trial of Macitentan\/Tadalafil single-tablet combination therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2024;83:473\u201384. https:\/\/doi.org\/10.1016\/J.Jacc.2023.10.045.","journal-title":"J Am Coll Cardiol"},{"key":"3525_CR19","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/J.Jacc.2021.07.057","volume":"78","author":"Km Chin","year":"2021","unstructured":"Chin KM, Sitbon O, Doelberg M, Feldman J, Gibbs J, Gr\u00fcnig E, et al. Three- versus two-drug therapy for patients with newly diagnosed pulmonary arterial hypertension. J Am Coll Cardiol. 2021;78:1393\u2013403. https:\/\/doi.org\/10.1016\/J.Jacc.2021.07.057.","journal-title":"J Am Coll Cardiol"},{"key":"3525_CR20","doi-asserted-by":"publisher","DOI":"10.1007\/S12325-024-02964-0","author":"Km Chin","year":"2024","unstructured":"Chin KM, Channick R, Kim NH, Macdonald G, Ong R, Martin N, et al. Macitentan and tadalafil combination therapy in incident and prevalent pulmonary arterial hypertension: real-world evidence from the Opus\/Orpheus studies. Adv Ther. 2024. https:\/\/doi.org\/10.1007\/S12325-024-02964-0.","journal-title":"Adv Ther"},{"key":"3525_CR21","doi-asserted-by":"publisher","DOI":"10.1002\/Ejhf.3319","author":"Vv Mclaughlin","year":"2024","unstructured":"Mclaughlin VV, Sitbon O, Chin KM, Gali\u00e8 N, Hoeper MM, Kiely DG, et al. Initial combination therapy with macitentan and tadalafil in patients with pulmonary arterial hypertension, with and without cardiac comorbidities. Eur J Heart Fail. 2024. https:\/\/doi.org\/10.1002\/Ejhf.3319.","journal-title":"Eur J Heart Fail"},{"key":"3525_CR22","doi-asserted-by":"publisher","DOI":"10.1161\/Jaha.116.003896","volume":"5","author":"A Wei","year":"2016","unstructured":"Wei A, Gu Z, Li J, Liu X, Han Y, Pu J. Clinical adverse effects of endothelin receptor antagonists: insights from the meta-analysis of 4894 patients from 24 randomized double-blind placebo-controlled clinical trials. J Am Heart Assoc. 2016;5:E003896. https:\/\/doi.org\/10.1161\/Jaha.116.003896.","journal-title":"J Am Heart Assoc"},{"key":"3525_CR23","unstructured":"Opsynvi\u00ae Macitentan & Tadalafil Single-Tablet Combination. Full Prescribing Information. Actelion Pharmaceuticals Us, Inc. March 2024."},{"key":"3525_CR24","unstructured":"Yuvanci\u00ae (Macitentan\/ Tadalafil) Summary of product characteristics. September 2024."},{"key":"3525_CR25","doi-asserted-by":"publisher","first-page":"4374","DOI":"10.1007\/S12325-022-02199-X","volume":"39","author":"R Souza","year":"2022","unstructured":"Souza R, Delcroix M, Gali\u00e9 N, Jansa P, Mehta S, Pulido T, et al. Long-term safety, tolerability and survival in patients with pulmonary arterial hypertension treated with macitentan: results from the Seraphin open-label extension. Adv Ther. 2022;39:4374\u201390. https:\/\/doi.org\/10.1007\/S12325-022-02199-X.","journal-title":"Adv Ther"},{"key":"3525_CR26","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1056\/Nejmoa1213917","volume":"369","author":"T Pulido","year":"2013","unstructured":"Pulido T, Adzerikho I, Channick R, Delcroix M, Gali\u00e8 N, Ghofrani A, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369:809\u201318. https:\/\/doi.org\/10.1056\/Nejmoa1213917.","journal-title":"N Engl J Med"},{"key":"3525_CR27","doi-asserted-by":"publisher","unstructured":"Qadus S, Naser AY, Ofori-Asenso R, Ademi Z, Al Awawdeh S, Liew D. Adherence and discontinuation of disease-specific therapies for pulmonary arterial hypertension: a systematic review and meta-analysis. Am J Cardiovasc Drugs. 2023;23:19\u201333. https:\/\/doi.org\/10.1007\/S40256-022-00553-6.","DOI":"10.1007\/S40256-022-00553-6"},{"key":"3525_CR28","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1183\/13993003.01032-2015","volume":"46","author":"N Gali\u00e8","year":"2015","unstructured":"Gali\u00e8 N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 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). Eur Respir J. 2015;46:903\u201375. https:\/\/doi.org\/10.1183\/13993003.01032-2015.","journal-title":"Eur Respir J"},{"key":"3525_CR29","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/Eurheartj\/Ehv317","volume":"37","author":"N Gali\u00e8","year":"2016","unstructured":"Gali\u00e8 N, Humbert M, Vachi\u00e9ry Jl, Gibbs S, Lang I, Torbicki A, et al. 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). Eur Heart J. 2016;37:67\u2013119. https:\/\/doi.org\/10.1093\/Eurheartj\/Ehv317.","journal-title":"Eur Heart J"},{"key":"3525_CR30","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02024-2021","volume":"59","author":"Mm Hoeper","year":"2022","unstructured":"Hoeper Mm, Pausch C, Gr\u00fcnig E, Staehler G, Huscher D, Pittrow D, et al. Temporal trends in pulmonary arterial hypertension: results from the Compera registry. Eur Respir J. 2022;59:2102024. https:\/\/doi.org\/10.1183\/13993003.02024-2021.","journal-title":"Eur Respir J"},{"key":"3525_CR31","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1007\/S12325-023-02730-8","volume":"41","author":"A Muller","year":"2024","unstructured":"Muller A, Escribano-Subias P, Fernandes CC, Fontana M, Lange TJ, S\u00f6derberg S, et al. Real-world management of patients with pulmonary arterial hypertension: insights from Exposure. Adv Ther. 2024;41:1103\u201319. https:\/\/doi.org\/10.1007\/S12325-023-02730-8.","journal-title":"Adv Ther"},{"key":"3525_CR32","unstructured":"Johnson & Johnson Innovative Medicine. Clinical trial data transparency. https:\/\/innovativemedicine.jnj.com\/our-innovation\/clinical-trials\/transparency. Accessed March 2025."},{"key":"3525_CR33","unstructured":"Yale University. The yoda project. Accessed March 2025. http:\/\/yoda.yale.edu."}],"container-title":["Advances in Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-026-03525-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12325-026-03525-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-026-03525-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T08:38:05Z","timestamp":1778229485000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12325-026-03525-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["3525"],"URL":"https:\/\/doi.org\/10.1007\/s12325-026-03525-3","relation":{},"ISSN":["0741-238X","1865-8652"],"issn-type":[{"value":"0741-238X","type":"print"},{"value":"1865-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]},"assertion":[{"value":"11 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"H. James Ford reports grants from United Therapeutics, Merck, Gossamer Bio, Johnson & Johnson, Cereno and Enzyvant, consultancy fees from United Therapeutics, Merck, Enzyvant, Liquidia, Johnson & Johnson and Gossamer Bio, and a prior leadership role with the Pulmonary Hypertension Association. Kelly M. Chin served as a scientific committee member for Johnson & Johnson; received research grants\/support from Johnson & Johnson, Altavant, Acceleron, United Therapeutics, Pfizer, Merck, Gossamer Bio; received support for travel to meetings from Johnson & Johnson; and received consultancy fees from Johnson & Johnson, Altavant, Acceleron, United Therapeutics, Gossamer Bio and Merck. Fenling Fan served as a scientific committee member for Johnson & Johnson. Ekkehard Gr\u00fcnig  has received fees for lectures and\/or consultations from Bayer\/MSD, Ferrer, GEBRO, GSK, Johnson & Johnson and OMT. Research grants to his institution have been received from Acceleron, BayerHealthCare, MSD, Bellerophon, GossamerBio, GSK, Johnson & Johnson, Novartis, OMT, Pfizer, REATA and United Therapeutics outside the submitted work. Michael Friberg\n                      ,\n                      Jakob A. Hauser and Hany Rofael are employees of Johnson & Johnson. Matthieu Pannaux was an employee of a company contracted by Johnson & Johnson at the time of the work. Current affiliation: Sanofi, Vitry-Sur-Seine, France. Pavel Jansa has received fees and grants from Johnson & Johnson,\u00a0AOP Orphan, Bayer Healthcare, MSD and Arena Pharmaceuticals Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The A DUE study (including the OL period) was conducted in compliance with the Declaration of Helsinki. Ethical approval was received from the institutional review boards \/ independent ethics committees at each site (see Supplement). As previously described, an Independent Data Monitoring Committee monitored safety during the DB period of the study and an Independent Liver Safety Data Review Board assessed any hepatic adverse events of special interest (AESIs) that required further evaluation throughout the study [\n                      \n                      ]. A clinical events committee (CEC) reviewed and confirmed or rejected all reported potential mortality and morbidity (M\/M) events in a blinded fashion. Written informed consent was obtained from all patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}