Real-World Transitions from Parenteral, Inhaled, and Oral Prostacyclin-Class Therapies to Oral Treprostinil: Interim Data from the ADAPT Registry

Abstract

Background: Oral treprostinil (ORE) is approved for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and improve exercise capacity. ADAPT is an ongoing registry (NCT03045029) following patients after ORE initiation to collect real-world use and tolerability, including site-and patient-reported data. This analysis reports characteristics and dosing data on patients transitioning from inhaled, parenteral, or oral prostacyclin class therapies (PCY) to ORE. Methods: As of July 26, 2019, interim data are reported for eligible patients who newly or previously (within 182 days) initiated ORE. Baseline data include the most recent variables collected the 182 days prior to ORE initiation. Data was prospectively collected for up to 78 weeks after ORE initiation. Analyses represent data from transition patients (receiving another PCY within 3 days prior to initiating ORE) and non-transition patients. Adverse event (AE) and dosing data were reported by patients in the online portal; if dosing data was provided without accompanying AE data at a given timepoint, it was assumed no AE occurred. Data were analyzed using descriptive statistics. Results: Data for 76 patients who initiated ORE, 27 (36%) of which transitioned from PCY, are reported. In transition patients, the median [IQR] time since diagnosis was 4.2 [2.3,8.7] years and median duration of previous PCY was 29.9 [9.9,59.5] months. Reasons for transition included convenience (n=10), tolerability (n=2), efficacy (n=4), worsening of disease (n=5), and other (n=6). At ORE initiation, 11%, 37%, and 52% were on none, one, or two PAH-specific background therapies, respectively. 56% of patients transitioned from parenteral treprostinil, 22% from inhaled treprostinil, 19% from selexipag, and 4% from epoprostenol. Of those with available patient-reported data, transition patients reported higher median [IQR] total daily dose (TDD) of ORE at initiation (3 [0.4,12] mg vs. 0.4 [0.4,0.9] mg),

Oral Prostacyclin Pathway Agents Used in PAH: A Targeted Literature Review

“…Studies from the ADAPT registry describe oral treprostinil use within triple combination (33.3% to 45.7% of patients receiving oral treprostinil). 28,29 However, neither of the early oral treprostinil trials, FREEDOM-C and FREEDOM-C2, demonstrated an improvement in 6MWD with the addition of oral treprostinil to double oral combination therapy (see Table 2). 16,17…”

Implementing the EXPEDITE parenteral induction protocol: Rapid parenteral treprostinil titration and transition to oral treprostinil

“…20 Real-world data describe these transitions; however, routes of administration, transition duration, and transition setting vary. 18,[21][22][23] Later, a case report in a prostacyclin naïve patient introduced the concept for rapid parenteral induction initiated while inpatient over approximately 1 week before treatment with oral treprostinil. 24 Parenteral induction occurred over 7 days and reached parenteral treprostinil dose of 42 ng/kg/min before transitioning to oral treprostinil dose of 24 mg TDD.…”

“…Of the 33 patients, 31 patients successfully transitioned and completed the 24‐week study while maintaining their hemodynamic statuses 20 . Real‐world data describe these transitions; however, routes of administration, transition duration, and transition setting vary 18,21–23 …”

“… 20 Real‐world data describe these transitions; however, routes of administration, transition duration, and transition setting vary. 18 , 21 , 22 , 23 …”