Treprostinil rapid-induction protocol yields improvements using expanded 4-strata risk stratification model
Presenter: Veronica Franco, MD, Ohio State University, Columbus, OH
Risk status improvements observed after parenteral induction and transition to oral treprostinil: A post-hoc analysis of the EXPEDITE study using the 4-strata risk model. Pulmonary Vascular Disease Posters 3. Presented Oct 10, 2023.
https://journal.chestnet.org/article/S0012-3692(23)04827-4/fulltext
A treprostinil rapid-induction protocol that used a shortened interval of parenteral treprostinil followed by oral treprostinil led to a more patients with pulmonary arterial hypertension (PAH) achieving low-risk status after 16 weeks than worsened, according to this study presented at the CHEST 2023 meeting. Patients’ functional risk levels were determined using the expanded 4-strata risk stratification model recommended in recent PAH guidelines.
In this post hoc analysis of the EXPEDITE study, initiating oral treprostinil after a short interval of parenteral treprostinil (titrated for 2-8 weeks) resulted in improved overall patient functional status when applying the 4-strata risk model recommended in the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, according to presenter Veronica Franco, MD, Ohio State University, Columbus, Ohio, and study coauthors in a poster presentation of the results.
“These results support rapid parenteral treprostinil induction to quickly reach clinically effective doses of oral treprostinil in patients with PAH,” said Dr Franco.
Continued titration of oral treprostinil beyond 16 weeks may augment the clinical benefits seen in the EXPEDITE study. The PAH guidelines recommend a risk-based approach to treatment with a goal of achieving and maintaining low-risk status, researchers said.
Oral treprostinil is approved for the treatment of patients with PAH to delay disease progression and improve exercise capacity. In the EXPEDITE study, a single-arm, multicenter trial, researchers showed that patients starting oral treprostinil after a short parenteral course of the drug could achieve high daily doses of oral treprostinil at week 16.
The study also showed that this treatment approach improved risk stratification from the 2015 ESC/ERS guidelines. Those 2015 guidelines said PAH should be stratified as low, intermediate, or high risk of mortality, based on World Health Organization Functional Class (WHO FC), N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk distance, and right atrial area.
The post hoc analysis of EXPEDITE presented at this 2023 CHEST annual meeting took into account changes from the 2022 guidelines, which comprise 4 risk categories (low, intermediate-low, intermediate-high, and high) and include WHO FC, NT-proBNP, and 6MWD as risk determinants.
The post hoc analysis included 28 of the 29 patients in the per-protocol population who were receiving oral treprostinil at week 16. Of those, 17 (61%) were female, 23 (82%) were white, and they were split 50-50 between WHO FC II and III (14 patients in each group).
From baseline to week 16, WHO FC improved in 39% of the patients, worsened in 4%, and stayed the same in 57%, the data show. Similarly, NT-proBNP improved in 39%, worsened in 11%, and was maintained in 50%. And for 6-minute walk distance, 26% improved, while 7% worsened and 67% remained stable.
Putting those 3 variables together, the mean composite risk score decreased from 2.0 to 1.0, respectively, for baseline and week 16. Going by the risk stratification in the latest guidelines, that represents a shift overall from intermediate-low to low risk, the investigators said.
Disclosures
The study was sponsored by United Therapeutics Corporation. In her disclosure, Veronica Franco reported no relationships pertinent to this presentation.
References
Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension [published correction appears in Eur Heart J. 2023; 44(15):1312]. Eur Heart J 2022; 43(38):3618-3731. doi:10.1093/eurheartj/ehac237
White RJ, Jerjes-Sanchez C, Bohns Meyer GM, et al. Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial. Am J Respir Crit Care Med 2020; 201(6):707-717. doi:10.1164/rccm.201908-1640OC
Miller CE, Franco V, Smith JS, et al. Parenteral treprostinil induction for rapid attainment of therapeutic doses of oral treprostinil. Respir Med 2023; 218:107374. doi:10.1016/j.rmed.2023.107374