Safety, tolerability and clinical effects of a rapid dose titration of subcutaneous treprostinil therapy in pulmonary arterial hypertension: a prospective multi-centre trial.

Background: The objective of this open label, multi-centre study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous (SC) treprostinil using pro-active infusion site pain management in patients with severe pulmonary arterial hypertension (PAH).

Methods: Safety and tolerability were assessed by adverse events and discontinuation rate. Clinical parameters and right heart catheterisation were performed at baseline and after 16 weeks.

Results: Thirty-nine patients with idiopathic, heritable or drug-induced PAH who were on stable treatment with oral PAH approved drugs (90% on dual combination therapy) were included. Patients achieved a mean dosage of 35.7 ng/kg/min of treprostinil after 16 weeks. Treatment was shown to be well tolerated by the majority of patients and was associated with a good overall safety profile. Three patients (8%) withdrew from treatment due to infusion site pain, which occurred in 92% during the course of the study. After 16 weeks, median 6 minute walking distance, cardiac index, pulmonary vascular resistance and tricuspid annular plane systolic excursion improved significantly.

Conclusion: Rapid dose titration of SC treprostinil was generally well-tolerated and achieved a clinically effective dose associated with significant improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may contribute to a successful treatment outcome in patients with severe PAH.