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 :