Abstract:
Selexipag is an oral selective prostacyclin receptor agonist, that was
approved for use in patients with NYHA functional class II-III pulmonary
arterial hypertension (PAH). In the GRIPHON study, selexipag
demonstrated consistent efficacy for individualised doses in low, medium
and high dose stratums. In order to better understand the real world
approach to selexipag titration and to establish the individualised
maintenance regimens used in our centre, we performed this retrospective
study of the first 20 patients prescribed selexipag. Baseline
characteristics differed from the GRIPHON study, with more combination
therapy and comorbidities at baseline; however. Maintenance doses were
stratified as low-dose in 10% (n=2), medium-dose in 70% (n=14) and
high-dose in 20% (n=4). Furthermore, two of these patients were
successfully transitioned from inhaled iloprost. This study demonstrates
that selexipag can be safely initiated, titrated and transitioned in an
outpatient setting to achieve an individualised dosing regimen.
Introduction :
Pulmonary arterial hypertension (PAH) is a devastating disease
characterised by irreversible pulmonary vascular proliferation and
remodelling resulting ultimately in right heart failure. Current therapy
targets the nitric oxide, endothelin and prostacyclin pathways to
promote pulmonary vasodilatation and reduce right ventricular afterload.1,
2 Selexipag is an oral selective
prostacyclin receptor agonist that is used in the treatment of PAH. In
the GRIPHON trial the optimum dose of selexipag for maximum therapeutic
benefit was determined to be the maximum tolerated dose for each
individual patient. It is postulated that the dose differs between
patients due to variations in prostacyclin (IP) receptor expression and
density.3-5 The
initiation dose of 200μg twice daily is prescribed and titrated weekly
until a total daily dose of 3200μg is achieved or side effects become
intolerable and an individual maximum tolerated dose is established. In
the GRIPHON study this strategy demonstrated consistent efficacy for
patients receiving low, medium or high selexipag
doses.6 In clinical
trials selexipag demonstrated improvements in six minute walk distance
(6MWD), n-terminal pro–brain natriuretic peptide (NT-proBNP), cardiac
index (CI) and pulmonary vascular resistance (PVR), and a significant
reduction was noted in the composite morbidity and mortality endpoint at
a median of 70.7 weeks of treatment.6,
7 In order to better understand the real
world approach to selexipag titration we performed a retrospective
analysis of the clinical and treatment characteristics of the first 20
patients prescribed selexipag in our centre.
Aim :
To perform a retrospective analysis of the clinical and treatment
characteristics of the first 20 patients prescribed selexipag in our
centre, with specific reference to drug titration and individualised
maintenance doses.
Materials and Methods :
This study received ethical approval from the institutional ethical
review board (IRB:1/378/2179 TMR). A retrospective search of the
hospital database was performed to identify patients with confirmed PAH
who commenced selexipag therapy, outside of a clinical trial, up until
June 2020. Paper charts and the hospital information technology service
(PatientCentre) were used to collect data that was subsequently fully
anonymised. Patients were excluded if they were commenced on selexipag
therapy in the context of a clinical trial, as their experience might
not reflect ‘real world’ practice.
Data regarding patient demographics, PAH subtype, duration of PAH
diagnosis, co-morbidities and regular medications were collected
retrospectively. New York Heart Associated (NYHA) functional class (FC),
patient risk stratification category (using the 2015 ESC/ERS PAH
guidelines risk table) and 6MWD were also
recorded.2. Details
regarding selexipag indication, titration, maintenance doses, reported
side effects and compliance were also recorded from patient records.
Statistical analysis was performed using GraphPad online statistical
software. Fisher’s exact test was employed to assess the statistical
significance for categorical variables and t-test was used to calculate
significance between means. A value < 0.05 was considered
statistically significant (P < 0.05).
Results :