Impact of selexipag maintenance dose on persistence, adherence, and hospitalization in US patients with pulmonary arterial hypertension

Selexipag is an oral selective agonist of the prostacyclin receptor approved to treat adults with pulmonary arterial hypertension (PAH). Selexipag is initiated at a dose of 200 μg twice daily (bid) and usually titrated up by 200 μg bid weekly (per label) or more slowly (e.g., every other week in real-world clinical practice) to the highest tolerated individualized dose (ID) ranging from 200 to 1600 µg bid. In the Phase 3 GRIPHON trial, selexipag delayed disease progression and reduced risk of PAH-related hospitalization compared with placebo; the effect was consistent across three prespecified ID groups: low (200-400 µg bid), medium (600-1000 µg bid), and high (1200-1600 µg bid). This study evaluated patient outcomes across selexipag dose ranges in real-world practice. Data were analyzed from 1186 US adult patients with PAH on selexipag from the Komodo closed-claims database (2015‒2022). Of these, 634 (53.5%) patients completed titration and reached their selexipag ID (43.8% high ID, 29.8% medium ID, 26.3% low ID). Subsequently, 72.4% of patients in the low ID group had dose adjustments compared with 61.9% (medium ID) and 34.5% (high ID; standardized mean difference 0.63). There were no significant differences in patient outcomes, i,e, persistence (time to discontinuation) and risk of all-cause and PAH-related hospitalization across ID groups. The findings in this diverse, real-world population of patients with PAH reinforced an individualized approach to the dosing scheme to maximize benefit-risk and achieve the highest tolerated dose with selexipag similar to findings from the GRIPHON trial and other studies.