Long‐Term Therapy with Oral Treprostinil in Pulmonary Arterial Hypertension Failed to Lead to Improvement in Important Physiologic Measures: Results from a Single Center

Abstract

Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = −0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose.

Long‐term study of oral treprostinil to treat pulmonary arterial hypertension: dosing, tolerability, and pharmacokinetics

“…17 When participants used BID drug, doses were essentially unchanged between Year 2 and Year 3. This is similar to the recently published experience from Chin et al, 19 except that those prostacyclin-experienced investigators achieved higher average TDD at 2 years than the global cohort reported here (9 mg at 12 months;…”

Update in Pulmonary Vascular Disease 2015

“…Similarly, the efficacy of oral treprostinil (42), which was approved by the U.S. Food and Drug Administration in 2013 based on the FREEDOM-M (Oral Treprostinil as Monotherapy for the Treatment of PAH) trial (43), was challenged by findings from a single-center study of patients enrolled in either FREEDOM-M or FREEDOM-C (Oral Treprostinil in Combination with an ERA [endothelin receptor antagonist] and/or a PDE-5I [phosphodiesterase type 5 inhibitor] for the Treatment of PAH). This study found no significant changes in 6-MWD, functional class, or hemodynamics when oral treprostinil was used at a rather low mean daily dose of 8.6 mg (44). Higher dose was correlated with lower PVR in that study, and more recent experience suggests increased dose frequency (three times daily instead of twice daily) allows for higher total daily dose with fewer doselimiting prostanoid side effects.…”

Pulmonary hypertension

“…Long-term riociguat had a favourable benefit-risk profile and showed sustained benefits in exercise and functional capacity for up to 1 year [22]. Single-centre experience with the results of balloon pulmonary angioplasty for inoperable CTEPH is promising.…”