학술논문
Long-Term Safety, Tolerability and Survival in Patients with Pulmonary Arterial Hypertension Treated with Macitentan: Results from the SERAPHIN Open-Label Extension.
Document Type
Academic Journal
Author
Souza R; Pulmonary Division, Heart Institute (INCOR), University of Sao Paulo, Av.Dr. Eneás de Carvalho Aguiar, 255, sala 7079, Sao Paulo, SP, CEP 06.403-010, Brazil. souza.rogerio@me.com.; Delcroix M; Clinical Department of Respiratory Diseases, Centre of Pulmonary Vascular Diseases, University Hospitals of Leuven, Leuven, Belgium.; BREATHE, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium.; Galié N; IRCCS-S Orsola University Hospital, Bologna, Italy.; Jansa P; 2nd Department of Internal Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.; Mehta S; Southwest Ontario PH Clinic, Respirology Division, London Health Sciences Centre, Western University, London, ON, Canada.; Pulido T; Department of Clinical Research, Ignacio Chávez National Heart Institute, Mexico City, Mexico.; Rubin L; University of California, San Diego Medical School, San Diego, CA, USA.; Sastry BKS; CARE Hospitals, Hyderabad, India.; Simonneau G; Hôpital Bicêtre, Université Paris-Sud, Le Kremlin Bicêtre, France.; Sitbon O; Hôpital Bicêtre, Université Paris-Sud, Le Kremlin Bicêtre, France.; Torbicki A; Department of Pulmonary Circulation, Thromboembolic Disease and Cardiology, Centre for Postgraduate Medical Education, ECZ-Otwock, Otwock, Poland.; Boyanova N; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.; Chamitava L; VALOS S.r.L, Genoa, Italy.; Stein C; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.; Channick RN; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Source
Publisher: Health Communications Inc Country of Publication: United States NLM ID: 8611864 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1865-8652 (Electronic) Linking ISSN: 0741238X NLM ISO Abbreviation: Adv Ther
Subject
Language
English
Abstract
Introduction: In SERAPHIN, a long-term, event-driven, double-blind randomised controlled trial in pulmonary arterial hypertension (PAH), macitentan 10 mg significantly reduced the risk of morbidity/mortality compared with placebo. Its open-label extension study (SERAPHIN OL) further assessed long-term safety and tolerability of macitentan 10 mg in PAH patients.
Methods: Patients in SERAPHIN who completed the double-blind treatment period or experienced a morbidity event during the study could enter SERAPHIN OL. Patients received macitentan 10 mg once daily, and safety and survival were assessed until end of treatment (+ 28 days). Two overlapping sets were analysed for safety: (1) all patients in SERAPHIN OL (OL safety set); (2) patients randomised to macitentan 10 mg in SERAPHIN (long-term safety/survival set). Survival was evaluated as an exploratory endpoint in the latter set.
Results: Of 742 patients randomised in SERAPHIN, 550 (74.1%) entered SERAPHIN OL (OL safety set); 242 patients were randomised to macitentan 10 mg in SERAPHIN (long-term safety/survival set). Median (min, max) exposure to macitentan 10 mg was 40.1 (0.1, 130.5) months (2074.7 patient-years; OL safety set) and 54.7 (0.1, 141.3) months (1151.0 patient-years; long-term safety/survival set). Safety in both analysis sets was comparable to the known safety profile of macitentan. Kaplan-Meier survival estimates (95% CI) at 1, 5, 7 and 9 years were 95.0% (91.3, 97.1), 73.3% (66.6, 78.9), 62.6% (54.6, 69.6) and 52.7% (43.6, 61.0), respectively (long-term safety/survival set; median follow-up: 5.9 years).
Conclusions: This analysis provides the longest follow-up for safety and survival published to date for any PAH therapy. The safety profile of macitentan 10 mg over this extensive treatment period was in line with that observed in SERAPHIN. As the majority of patients were receiving other PAH therapy at macitentan initiation, our study provides additional insight into the long-term safety of macitentan, including as part of combination therapy.
Trial Registration: ClinicalTrials.gov Identifiers: NCT00660179 and NCT00667823.
(© 2022. The Author(s).)
Methods: Patients in SERAPHIN who completed the double-blind treatment period or experienced a morbidity event during the study could enter SERAPHIN OL. Patients received macitentan 10 mg once daily, and safety and survival were assessed until end of treatment (+ 28 days). Two overlapping sets were analysed for safety: (1) all patients in SERAPHIN OL (OL safety set); (2) patients randomised to macitentan 10 mg in SERAPHIN (long-term safety/survival set). Survival was evaluated as an exploratory endpoint in the latter set.
Results: Of 742 patients randomised in SERAPHIN, 550 (74.1%) entered SERAPHIN OL (OL safety set); 242 patients were randomised to macitentan 10 mg in SERAPHIN (long-term safety/survival set). Median (min, max) exposure to macitentan 10 mg was 40.1 (0.1, 130.5) months (2074.7 patient-years; OL safety set) and 54.7 (0.1, 141.3) months (1151.0 patient-years; long-term safety/survival set). Safety in both analysis sets was comparable to the known safety profile of macitentan. Kaplan-Meier survival estimates (95% CI) at 1, 5, 7 and 9 years were 95.0% (91.3, 97.1), 73.3% (66.6, 78.9), 62.6% (54.6, 69.6) and 52.7% (43.6, 61.0), respectively (long-term safety/survival set; median follow-up: 5.9 years).
Conclusions: This analysis provides the longest follow-up for safety and survival published to date for any PAH therapy. The safety profile of macitentan 10 mg over this extensive treatment period was in line with that observed in SERAPHIN. As the majority of patients were receiving other PAH therapy at macitentan initiation, our study provides additional insight into the long-term safety of macitentan, including as part of combination therapy.
Trial Registration: ClinicalTrials.gov Identifiers: NCT00660179 and NCT00667823.
(© 2022. The Author(s).)