Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial.
BACKGROUND
Pulmonary arterial hypertension (PAH) leads to reduced health-related quality of life (HRQoL). The objectives of this analysis were to evaluate the effect of macitentan on HRQoL in patients with PAH in the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) study. The association between baseline HRQoL and long-term outcomes was also investigated.


METHODS
Patients were randomized to placebo, macitentan 3 mg, or macitentan 10 mg once daily. Patients aged 14 years or older completed the 36-Item Short Form Survey (SF-36) at baseline, at month 6 and month 12, and at the end of treatment (EOT). The absolute change from baseline to month 6 in SF-36 scores was calculated. The time to a clinically meaningful deterioration in the SF-36 physical component summary and mental component summary (PCS and MCS) scores and associations between baseline PCS/MCS scores and time to morbidity/mortality events were also assessed.


RESULTS
At month 6, macitentan 10 mg significantly improved seven of eight SF-36 domains and the PCS and MCS scores vs placebo. Macitentan 10 mg significantly reduced the risk of a three-point or greater deterioration in PCS (hazard ratio [HR], 0.60; 95% CI, 0.47-0.76; P < .0001) and MCS scores (HR, 0.76; 95% CI, 0.61-0.95; P = .0173) until EOT vs placebo. Patients with a baseline PCS score greater than the median baseline value had a significantly reduced risk of morbidity/mortality compared with patients with a PCS score less than the median; a similar result was observed for the MCS score.


CONCLUSIONS
Macitentan significantly improved HRQoL in patients with PAH compared with placebo and significantly reduced the risk of a clinically meaningful HRQoL deterioration. An association between better baseline HRQoL and improved long-term outcomes was shown.


BACKGROUND
ClinicalTrials.gov; No.: NCT00660179; URL: clinicaltrials.gov.
London Health Sciences Centre, Victoria Hospital, Western University, London, ON, Canada. Electronic address: sanjay.mehta@lhsc.on.ca.
Sanjay
S
Mehta
CARE Hospitals, Hyderabad, India.
Bhagavatula Kutumba Srinivasa
BKS
Sastry
Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
Rogério
R
Souza
Centre of Postgraduate Medical Education, Europejskie Centrum Zdrowia, Otwock, Poland.
Adam
A
Torbicki
University of Giessen and Marburg Lung Center, Giessen, Germany, Member of the German Center of Lung Research (DZL), Giessen, Germany, and Department of Medicine, Imperial College London, London, England.
Hossein-Ardeschir
HA
Ghofrani
Massachusetts General Hospital, Boston, MA.
Richard N
RN
Channick
Gasthuisberg University Hospital, Leuven, Belgium.
Marion
M
Delcroix
Ignacio Chávez National Heart Institute, Mexico City, Mexico.
Tomás
T
Pulido
Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France, and INSERM U-999, Centre chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Gérald
G
Simonneau
John Wlodarczyk Consulting Services, Newcastle, Australia.
John
J
Wlodarczyk
University of California, San Diego Medical School, San Diego, CA.
Lewis J
LJ
Rubin
Charles University, Prague, Czech Republic.
Pavel
P
Jansa
Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Elke
E
Hunsche
Bologna University Hospital, Bologna, Italy.
Nazzareno
N
Galiè
Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Loïc
L
Perchenet
Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France, and INSERM U-999, Centre chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Olivier
O
Sitbon
D000328:Adult; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D065131:Endothelin B Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D008297:Male; D008875:Middle Aged; D062072:Patient Acuity; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D065131:Endothelin B Receptor Antagonists; D011743:Pyrimidines; D013449:Sulfonamides; C533860:macitentan
health-related quality of life; pharmacotherapy; pulmonary arterial hypertension