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

Abstract

RATIONALE:

Oral 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.

OBJECTIVES:

EXPEDITE (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.

METHODS:

Parenteral 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.

RESULTS:

Twenty-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.

CONCLUSION:

Short-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.

• Authors: Chad E Miller, Veronica Franco, Jimmy S Smith, Vijay Balasubramanian, John Kingrey, Ronald Zolty, Lana Melendres-Groves, Jessica Huston, Jean M Elwing, Ashwin Ravichandran, Dana Cella, Eric Shen, Scott Seaman, Claire M Thrasher, Meredith Broderick, Ronald J Oudiz
• Journal: Respiratory medicine (Respir Med) Vol. 218 Pg. 107374 (11 2023) ISSN: 1532-3064 [Electronic] England
• PMID: 37532157 (Publication Type: Clinical Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antihypertensive Agents
• Epoprostenol
• treprostinil

Topics

• Humans
• Antihypertensive Agents
• Epoprostenol
• Familial Primary Pulmonary Hypertension (drug therapy)
• Hypertension, Pulmonary (drug therapy)
• Pulmonary Arterial Hypertension (drug therapy)
• Treatment Outcome