TY - JOUR
T1 - Current therapies for the treatment of systemic sclerosis-related pulmonary arterial hypertension
T2 - Efficacy and safety
AU - Murdaca, Giuseppe
AU - Spanò, Francesca
AU - Puppo, Francesco
PY - 2014/3
Y1 - 2014/3
N2 - Introduction: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. Patients with limited SSc typically develop pulmonary arterial hypertension (PAH). TNF-α, VEGF, platelet-derived growth factor and endothelin-1 play a key role in the development of PAH. Areas covered: This paper addresses the efficacy and safety of current drugs used for the treatment of PAH. Expert opinion: Bosentan, ambrisentan, sildenafil, tadalafil, iloprost, epoprostenol and treprostinil were associated with hemodynamic improvements in PAH patients. Ambrisentan has a better safety profile compared with bosentan, regarding the risk of increase in hepatic transaminases. Flushing, dyspepsia and diarrhea were the most frequent adverse events in patients treated with sildenafil, while headache, myalgia and flushing were the adverse events in those receiving tadalafil. Inhaled iloprost is also effective, but it requires multiple daily nebulizations up to 15 min each and may induce cough, flushing, jaw pain and headache. Epoprostenol is considered the most effective approved therapy for severe PAH in WHO functional class III and class IV. TNF-α inhibitors reduce the systemic inflammation in patients with chronic immune-mediated diseases and improve the endothelial function, decreasing the risk of PAH progression.
AB - Introduction: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. Patients with limited SSc typically develop pulmonary arterial hypertension (PAH). TNF-α, VEGF, platelet-derived growth factor and endothelin-1 play a key role in the development of PAH. Areas covered: This paper addresses the efficacy and safety of current drugs used for the treatment of PAH. Expert opinion: Bosentan, ambrisentan, sildenafil, tadalafil, iloprost, epoprostenol and treprostinil were associated with hemodynamic improvements in PAH patients. Ambrisentan has a better safety profile compared with bosentan, regarding the risk of increase in hepatic transaminases. Flushing, dyspepsia and diarrhea were the most frequent adverse events in patients treated with sildenafil, while headache, myalgia and flushing were the adverse events in those receiving tadalafil. Inhaled iloprost is also effective, but it requires multiple daily nebulizations up to 15 min each and may induce cough, flushing, jaw pain and headache. Epoprostenol is considered the most effective approved therapy for severe PAH in WHO functional class III and class IV. TNF-α inhibitors reduce the systemic inflammation in patients with chronic immune-mediated diseases and improve the endothelial function, decreasing the risk of PAH progression.
KW - Anti-endothelin-1
KW - Phosphodiesterase type 5 inhibitors
KW - Prostanoids
KW - Systemic sclerosis-related pulmonary arterial hypertension
KW - TNF-α inhibitors
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U2 - 10.1517/14740338.2014.872238
DO - 10.1517/14740338.2014.872238
M3 - Article
C2 - 24387049
AN - SCOPUS:84896735712
VL - 13
SP - 295
EP - 305
JO - Expert Opinion on Drug Safety
JF - Expert Opinion on Drug Safety
SN - 1474-0338
IS - 3
ER -