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Multi-center Experience with the Transition to Treprostinil from Inhaled Iloprost in Pulmonary Arterial Hypertension

Robert Frantz


Michael McGoon


Aaron Waxman


Nick Kim


Fernando Torres


D. Strootman

K. Rollins

Steven Nathan


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Conference: 2008 International PHA Conference and Scientific Sessions

Release Date: 06.20.2008

Presentation Type: Abstracts

Frantz R., McGoon M., Waxman A., Kim N., Torres F., Rollins K., Strootman D., Nathan S.

Mayo Clinic, USA, Massachusetts General Hospital, USA, University of California San Diego, USA, University of Texas Southwestern, USA, United Therapeutics Corp, USA, Inova Fairfax Hospital, USA

BACKGROUND: Transition to parenteral treprostinil (TRE) from inhaled iloprost ( ILO) in pulmonary arterial hypertension patients has not been studied. We conducted a retrospective chart review at five US centers to provide best-practice insight on procedure, safety and long-term outcomes of transition.

METHODS: We reviewed 24 medical records to determine reason for transition, transition procedure, dose titrations, and clinical outcomes.

RESULTS: To date, data from 24 patients (12 idiopathic, 7 collagen vascular disease-associated, 2 congenital defect, 1 PoPAH and 2 ILD with PH) at 4 centers have been collected. Mean duration of PAH at transition was 3.3 years (range 0.1-15.1 years). Mean duration on ILO was 37.2 (SD±21.9) weeks and ranged 6.1-118.6 weeks. The primary reason for transition was worsening PAH symptoms in all patients. Non-compliance with ILO dosing was a secondary reason in four patients. Additional background therapy included thirteen patients receiving bosentan and sildenafil, five on sildenafil alone, and 2 on bosentan alone at the time of the transition. Mean daily dose of ILO at transition was 30.8 mcg. Eight patients were transitioned to TRE at home and two were started in the outpatient clinic; fourteen started in hospital with four transitioned emergently. Twelve patients discontinued ILO up to 48 hours prior to dosing TRE, one patient discontinued 3 months prior to TRE, and eleven patients continued ILO 2.5 mcg 2-4 times per day as needed for  dyspnea during early titration for up  to a mean of 10.5 days (range 1-49 days). TRE was started at 1.25-5 ng/kg/min with a mean dose 7.8 ng/kg/min two weeks after transition and last reported mean dose of 53.7 ng/kg/min (±36.3).  There were twelve patients with a 6MWD on ILO and TRE.  The mean ILO 6MWD was 267.1 (±128.8)m at a mean of 25.5 weeks on ILO. The mean first recorded 6MWD on TRE was 304.8 (±113.9)m at a mean of 13.0 weeks past transition and the most current 6MWD on TRE was 311.2 (±113.0)m at a mean of 46 weeks post transition.  There was a mean improvement at first reported 6MWD following the transition to TRE of 37.3 meters with a mean improvement of 44 meters at the most current 6MWD on TRE.  All patients were either WHO FC III or IV.  Six patients improved by at least one FC and three patients declined one FC.  No SAEs occurred as a result of the switch. Six patients died following transition to TRE (5 worsening PAH, one brain tumor). AEs pre and post switch were expected side effects associated with inhaled and parenteral prostacyclin.  No patients discontinued TRE following transition.   

CONCLUSIONS: Transition of patients experiencing worsening PAH to TRE from ILO appeared to be well tolerated. Experience from these centers provides guidance in transitioning high risk PAH patients on ILO to TRE.