PURPOSE: In its pivotal study, clinical benefit with the use of SQ treprostinil in PAH was mainly seen with a dose >14 ng/kg/min. However, only a small group of patients reached this dose by 3 months. We believe that such slow uptitration leads to an imbalance in most patients’ and clinicians perception of benefit: 3 or more months of potential substantial site pain while enjoying only a limited clinical benefit. Our experience suggests that a faster uptitration can be safely accomplished.
METHODS: We reviewed the data of patients with severe PAH seen at the Medical College of Wisconsin's PH Center and who underwent rapid inhospital uptitration.
RESULTS: We identified five consecutive patients between 5/06-4/07. Average age was 52. Sixty percent were male. Sixty-percent had idiopathic PAH and 40% were scleroderma-related. All patients were monitored in the intensive care unit. Dose was started at 2 ng/kg/min and was increased by 2 ng every 8-12 hours as tolerated by side effects and hemodynamics. Dose achieved during inpatient uptitration (ng/kg/min) and time to reach such dose: Patient One: 10 (4 days); Two: 14 (3 days); Three: 16 (4 days); Four: 16 (4 days); Five: 12 (4 days). Two patients developed severe headache which resolved with analgesics. Two patients required dose decrease of anti-hypertensive agents. There were no significant adverse hemodynamic effects. After discharge, dose continued to be increased by at least 2 ng/kg/min × week.
CONCLUSION: Our protocol appeared to be safe and was well tolerated. In <5 days, our patients achieved treatment doses that were reached by only a small number of patients in the pivotal study after at least 3 months of therapy.
CLINICAL IMPLICATIONS: Current data suggest that the strongest clinical benefit of SQ Treprostinil is seen with doses >40ng/kg/min. Given the time it takes to reach such dose with a “standard” uptitration protocol, a high rate of early discontinuation of therapy is likely to occur. Our rapid uptitration protocol could improve therapy adherence by reaching a more rapid clinical benefit.
DISCLOSURE: Francisco Soto, Consultant fee, speaker bureau, advisory committee, etc. Consultant fee, speaker bureau and/or advisory committee for Actelion Pharmaceuticals, Encysive Pharmaceuticals, Pfizer, Gilead and United Therapeutics; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The rapid uptitration protocol discussed in this abstract has not been prospectively studied yet.