Bosentan in systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a relatively rare chronic connective tissue disease characterized by varying degrees of skin fibrosis and visceral organ involvement. Pulmonary compromise, including pulmonary arterial hypertension and interstitial lung disease, is currently the leading cause of death in patients with SSc. Digital ulcers are common complications which lead to substantial morbidity and functional limitation. Until recently, treatment options for these complications were quite limited. Endothelin-1 (ET-1) is a peptide that has a role in promoting both vascular injury and the fibrotic process in SSc. Bosentan is a dual endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension. In patients with pulmonary hypertension secondary to SSc, bosentan therapy prevents deterioration in exercise capacity and may improve survival. No beneficial effect was found in one study in patients with interstitial lung disease and SSc. Bosentan is able to reduce the number of new digital ulcers in patients with either a history of previous ulcers or an active ulcer, without expediting the healing of existing ulcers. Bosentan therapy is contraindicated in pregnancy and causes elevated liver transaminases in up to 14% of patients. Hence, monthly pregnancy tests should be performed and hepatic function should be monitored.