Parenteral treprostinil induction for rapid attainment of therapeutic doses of oral treprostinil

Abstract

RationaleOral treprostinil slows disease progression and improves exercise capacity in pulmonary arterial hypertension; however, titration can be prolonged. Published data suggests prostacyclin-naïve patients achieve total daily oral treprostinil doses of about 6 mg by Week 16, while those on prior parenteral treprostinil reach higher doses at the same timepoint. ObjectivesEXPEDITE (NCT03497689), a single-arm, multicenter study, assessed the efficacy of rapid parenteral treprostinil induction to quickly reach higher doses of oral treprostinil for the treatment of pulmonary arterial hypertension. MethodsParenteral treprostinil was titrated for 2–8 weeks, followed by cross-titration of oral treprostinil. The primary endpoint was percentage of patients reaching ≥12 mg daily of oral treprostinil at Week 16. Secondary endpoints included clinical changes from baseline to Week 16. ResultsTwenty-nine prostacyclin-naïve patients were included in efficacy analyses. At Week 16, the mean daily oral treprostinil dose was 16.4 mg; 79% of patients met the primary endpoint. From baseline to Week 16, median REVEAL Lite 2 score improved (decreased) from 6 to 3.5 (p = 0.0006). Statistically significant improvements were also seen in World Health Organization Functional Class, N-terminal-pro brain natriuretic peptide levels, 6-minute walk distance, right atrial area, Borg Dyspnea Score, and emPHasis-10 score. Favorable trends were seen in risk stratification, echocardiography parameters, disease symptoms, and treatment satisfaction. ConclusionShort-course parenteral treprostinil induction resulted in oral treprostinil doses over twice those reported in de novo initiations and may be a useful approach to quickly achieve the therapeutic benefits of oral treprostinil.