Pneumologie 2018; 72(S 01): S78
DOI: 10.1055/s-0037-1619326
Sektion 6 – Kardiorespiratorische Interaktion
Posterbegehung – Titel: Kardiorespiratorische Interaktion in Ruhe, im Schlaf und unter Belastung
Georg Thieme Verlag KG Stuttgart · New York

Using controlled and real-world data in concert to assess survival in pulmonary arterial hypertension: Insights from SERAPHIN and REVEAL

A Ghofrani
1   Med. Klinik II/V, Universitätsklinikum Gießen und Marburg GmbH, Standort Gießen
,
R Benza
2   Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania
,
H Uno
3   Dana-Farber Cancer Institute, Boston, Massachusetts
,
R Channick
4   Massachusetts General Hospital; Harvard Medical School
,
M Delcroix
5   University Hospitals Leuven
,
H Farber
6   Boston University School of Medicine
,
N Galie
7   Istituto DI Malattie Dell'apparato Cardiovascolare, Università DI Bologna
,
B Hennessy
8   Actelion Pharmaceuticals Ltd, Allschwi, Switzerland
,
P Jansa
9   Charles University Prague
,
S Mehta
10   LHSC University Hospital, London, Ontario
,
L Perchenet
8   Actelion Pharmaceuticals Ltd, Allschwi, Switzerland
,
T Pulido
11   Ignacio Chávez National Heart Institute, Mexico City
,
D Rosenberg
8   Actelion Pharmaceuticals Ltd, Allschwi, Switzerland
,
L Rubin
12   Division of Pulmonary and Critical Care Medicine, University of California, San Diego Medical School
,
BKS Sastry
13   CARE Hospitals, Hyderabad, India
,
G Simonneau
14   Hôpital de Bicêtre, Univ. Paris-Sud
,
O Sitbon
15   Service de Pneumologie, Hôpital Bicêtre, Univ. Paris-Sud
,
R De Souza
16   Incor Heart Institute, University of Sao Paulo
,
LJ Wei
17   Harvard University, Boston, Massachusetts
,
A Torbicki
18   CMKP, ECZ-Otwock, Poland
› Author Affiliations
Further Information

Publication History

Publication Date:
21 February 2018 (online)

 

Designing a randomized controlled trial (RCT) to investigate a survival benefit in a rare disease such as pulmonary arterial hypertension (PAH) has considerable logistical and ethical constraints. In the SERAPHIN RCT, a 23% non-significant reduction in the risk of all-cause mortality was observed with macitentan 10 mg vs. placebo. As SERAPHIN enrolled patients in the same time frame as the US REVEAL registry, a prediction model based on REVEAL data was used to further explore the effect of macitentan on mortality. From REVEAL (N = 3515), 734 patients who would have met SERAPHIN eligibility criteria were selected (REVEAL analysis cohort [RAC]). Using the RAC, a prediction model for time to death up to 3 years was constructed based on ten baseline prognostic variables. The model was used to predict survival of each of the 742 SERAPHIN patients had they received real-world treatment in the RAC. The average temporal profile of these patients was then compared with the observed survival of the macitentan 10 mg group (n = 242) using a log-rank test and Cox's proportional hazard model. Over 3 years, the risk of mortality observed with macitentan 10 mg was 35% lower than that predicted (p = 0.01) (Fig). Real-world observational data can complement RCT data to provide a means of evaluating survival benefits in rare diseases. Merits and limitations of this approach will be discussed.

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Fig. 1: Survival comparison between macitentan 10 mg and predicted real-world treatment for the SERAPHIN population