Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases

Objective: Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue diseases (CTD), with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a group of patients with PAH related to CTD. Methods: Twelve patients with PAH related to systemic sclerosis (8 cases), SLE (2 cases), mixed connective tissue disease (1 case) and polymyositis (1 case) attending the Rheumatology Unit of Padova University were treated with bosentan for two years. Distance walked in 6 minutes, right ventricular systolic pressure and mean pulmonary artery pressure estimated by doppler echocardiography were evaluated at baseline and after 6, 12, 18 and 24 months of treatment. Safety was assessed by laboratory tests performed every two months. Results: During bosentan treatment, a significant decrease of right ventricular systolic pressure was observed after 6, 12, 18 and 24 months in comparison to baseline, whereas pulmonary artery mean pressure remained unchanged. Distance walked in 6 minutes slightly increased after 6 and 12 months, but significantly decreased after 18 and 24 months, mostly because complications of CTD which compromised the ability to walk arose in 4 patients. Adverse events related to bosentan were observed in 2 cases. Conclusions: Bosentan has been demonstrated effective in reducing pulmonary arterial pressure in a two-year period of treatment. Exercise capacity improved only in the first year of therapy and worsened thereafter, suggesting the opportunity of a combination therapy for a long-term treatment of PAH related to CTD.