INTRODUCTION: This study explored patient and clinician perspectives on a new fixed-dose combination of macitentan and tadalafil (M/T FDC) in a once-daily single tablet for treatment of pulmonary arterial hypertension (PAH). METHODS: Qualitative semi-structured interviews were conducted during the open-label period of the global, phase 3 A DUE clinical trial that evaluated M/T FDC. A subset of enrolled patients (N = 26) and site investigators (N = 18 clinicians) were interviewed. Patients received four tablets during double-blind treatment and could be in one of three arms (macitentan + placebo; tadalafil + placebo; M/T FDC + placebo) followed by M/T FDC (one tablet) during the open-label period. Patients and clinicians were asked to share their experience of pre-trial PAH medication, double-blind treatment, and open-label M/T FDC. Thematic analysis was conducted on blinded data. RESULTS: Patients preferred the M/T FDC tablet (open-label) over the four tablets during double-blind treatment. Patients were satisfied with M/T FDC, highlighting its positive impact on their psychological well-being, through reducing stress associated with managing multiple pills. All patients indicated that having a single, once-a-day pill for PAH was more convenient and associated with greater treatment adherence. Clinicians highlighted that their patients have a high daily pill burden for PAH and other comorbidities, and prefer treatments with an oral mode of administration that reduce the number of daily pills required. Clinicians felt that M/T FDC would be well received in clinical practice and potentially assist in implementing guideline-recommended combination treatment of PAH. CONCLUSIONS: In this qualitative analysis, all 26 patients and 18 clinicians provided positive feedback on M/T FDC treatment, which was consistent across countries. Reducing the number of pills needed to treat PAH, through use of single-tablet M/T FDC, is highly valued by patients and endorsed by clinicians, who both felt the single-tablet combination therapy could have a positive effect on patients' well-being and increase treatment adherence.

1st Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China

Charles University and General University Hospital Prague Czech Republic

Clinical Outcomes Solutions Chicago IL USA

Clinical Outcomes Solutions Folkestone UK

Janssen Cilag GmbH a Johnson and Johnson Company Neuss Germany

Janssen Cilag Limited a Johnson and Johnson Company Clinical Science Glasgow UK

Janssen Global Services LLC a Johnson and Johnson Company Horsham PA USA

Janssen Research and Development LLC a Johnson and Johnson Company Titusville NJ USA

Suite 8 Motis Business Centre Cheriton High Street Folkestone Kent T19 4QJ UK

Thoraxklinik at Heidelberg University Hospital Heidelberg Germany

Translational Lung Research Center Heidelberg Germany

UT Southwestern Medical Center Dallas TX USA

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Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43:3618–731. PubMed

Montani D, Gunther S, Dorfmuller P, et al. Pulmonary arterial hypertension. Orphanet J Rare Dis. 2013;8:97. PubMed PMC

Benza RL, Miller DP, Gomberg-Maitland M, et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation. 2010;122:164–72. PubMed

Kylhammar D, Persson L, Hesselstrand R, Radegran G. Prognosis and response to first-line single and combination therapy in pulmonary arterial hypertension. Scand Cardiovasc J. 2014;48:223–33. PubMed

Tonelli AR, Arelli V, Minai OA, et al. Causes and circumstances of death in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2013;188:365–9. PubMed PMC

Ibrahim E, Al-Akabawi A, Dawodu M, Ling J, Wang I, Millson B. Concomitant medication use in treatment journey of pulmonary arterial hypertension patient: a Canadian retrospective claims analysis. Am J Respir Crit Care Med. 2022;205:A5636.

Suárez JA, Manzaneque A, Garcia NC, Creus MT, Mir JB. DI-058 Risk of drug–drug interactions in a pulmonary arterial hypertension population. Eur J Hosp Pharm. 2017;24(Suppl 1):A138–9.

Grady D, Weiss M, Hernandez-Sanchez J, Pepke-Zaba J. Medication and patient factors associated with adherence to pulmonary hypertension targeted therapies. Pulm Circ. 2018;8:2045893217743616. PubMed PMC

Kjellström B, Sandqvist A, Hjalmarsson C, Nisell M, Näsman P, Ivarsson B. Adherence to disease-specific drug treatment among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. ERJ Open Res. 2020;6:00299–2020. PubMed PMC

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;23:19–33. PubMed

Grünig E, Jansa P, Fan F, et al. Randomized trial of macitentan/tadalafil single-tablet combination therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2024;83:473–84. PubMed

Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3:77–101.

Braun V, Clarke V. What can “thematic analysis” offer health and wellbeing researchers? Int J Qual Stud Health Well-being. 2014;9:26152. PubMed PMC

Galie N, Humbert M, Vachiery JL, 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;46:903–75. PubMed

Galiè N, Humbert M, Vachiery JL, 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;37:67–119. PubMed

Le Bozec A, Korb-Savoldelli V, Boiteau C, et al. Medication adherence, related factors and outcomes among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: a systematic review. Eur Respir Rev. 2024;33:240006. PubMed PMC

Frantz RP, Hill JW, Lickert CA, et al. Medication adherence, hospitalization, and healthcare resource utilization and costs in patients with pulmonary arterial hypertension treated with endothelin receptor antagonists or phosphodiesterase type-5 inhibitors. Pulm Circ. 2020;10:2045894019880086. PubMed PMC

Farber H, Germack H, Croteau N, et al. Real-world association between nonadherence to pulmonary arterial hypertension medications and clinical outcomes in the US. Chest. 2023;164:A5945–7.

Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to single-pill versus free-equivalent combination therapy in hypertension: a systematic review and meta-analysis. Hypertension. 2021;77:692–705. PubMed

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. J Health Econ Outcomes Res. 2024;11:8–22. PubMed PMC

Pugh ME, Hemnes AR. Pulmonary hypertension in women. Expert Rev Cardiovasc Ther. 2010;8:1549–58. PubMed PMC

Saleem M, Chowdhury M, Aggarwal A, Aina DA, Zughaib M. Gender differences in the cardiology fellowship interview experience. JACC Adv. 2024;3:100810. PubMed PMC