Abstract RATIONALE ESC/ERS Guidelines recommend discontinuing causative agents of suspected drug/toxin-associated pulmonary arterial hypertension (PAH) and treating similarly as other PAH etiologies. However, clinicians may hesitate to prescribe parenteral prostacyclin to patients with methamphetamine-associated PAH (meth-PAH) due to concerns regarding parenteral line care or misuse in the outpatient setting. EXPEDITE (NCT03497689) demonstrated that participants with PAH who received parenteral induction therapy achieved high oral treprostinil doses at Week 16 (79% achieved ≥12 mg daily). This post-hoc analysis evaluates clinical response in meth-PAH participants in EXPEDITE. Methods In EXPEDITE, parenteral treprostinil (subcutaneous/intravenous) was initiated, up-titrated for 2-8 weeks, then transitioned to oral treprostinil with further up-titration through Week 16. Initiation and transition could take place in the inpatient or outpatient setting. Differences in 6MWD, NT-proBNP, WHO FC, emPHasis-10 quality of life, and COMPERA 2.0 scores from Baseline to Week 16 are presented here for meth-PAH participants in EXPEDITE. Results are reported as median IQR. Results Four of the 29 per-protocol participants had meth-PAH. All were treated at one center and are included in this analysis. Age of this subgroup was 55 52, 57 years; one participant was female. Subcutaneous treprostinil was initiated in the inpatient setting and up-titrated to 40 ng/kg/min prior to transition in all four participants. Parenteral treprostinil exposure was 62 61, 63 days; cross-titration with oral treprostinil occurred over a median of 5 days. Oral treprostinil exposure was 64 59, 66 days. All participants completed EXPEDITE achieving 24 mg TDD oral treprostinil at Week 16. One participant enrolled in the optional extension study (ADAPT registry, NCT03045029) and maintained 24 mg TDD through completion of ADAPT (14 months). At Week 16, all four experienced decreases in NT-proBNP (-324 -769, -181 pg/mL) and improvement in emPHasis-10 quality of life score (-31 -32, -23) from Baseline. All reached WHO FC I at Week 16 (Table 1). All three participants with available data improved their 6MWD (+77 55, 95 m) and COMPERA 2.0 risk strata from Baseline to Week 16. During the parenteral phase, two participants experienced a serious AE (worsening dyspnea, worsening PAH) with both resolving. AEs were consistent with previously reported parenteral and oral treprostinil AEs. CONCLUSIONS EXPEDITE participants with meth-PAH successfully transitioned from parenteral to high-dose oral treprostinil with improvements to clinical parameters and quality of life. The EXPEDITE approach may be considered for meth-PAH patients when alternatives to parenteral administration are preferred. Sponsored by United Therapeutics. This abstract is funded by: United Therapeutics Corporation
Balasubramanian et al. (Fri,) studied this question.