Bosentan therapy for cutaneous fibrosis in systemic sclerosis

Background: Bosentan, an oral dual endothelin receptor antagonist, has shown to be effective in the treatment of pulmonary arterial hypertension (PAH) and ischaemic digital ulcers (IDU) in systemic sclerosis (SSc) patients. Some clinical reports also suggest a short-term benefit in treating Raynaud's phenomenon and cutaneous fibrosis (CF) in SSc patients. The aim of this case series was to describe the long-term benefit of bosentan in treating CF. Methods: In an open, non-controlled prospective case series, SSc patients were treated with bosentan (mean follow-up: 11 +/- 6.4 months) on standard doses. CF was assessed with the modified Rodnan Skin Score (mRSS). Results: Six patients had limited SSc (LSSc) and seven diffuse SSc (DSSc). Overall, 92% were women, mean age was 51 +/- 17 years and mean SSc duration was 12 +/- 7.7 years. Indications for treatment were SSc associated PAH (five patients) and unresponsive IDU (eight patients). All SSc patients experienced amelioration of CF, with a mean mRSS reduction of 46% (p = 0.001), 45.7% (p = 0.018) and 46.5% (p = 0.026) for the whole group, DSSc and LSSc, respectively. Improvement of skin was independent of the duration of SSc, baseline skin score and type of SSc. Generally, bosentan treatment was well tolerated. Three patients (23%) had an elevation of liver transaminases > 3 times above the upper limit of normal, including an acute symptomatic cholestatic hepatitis which led to patient's withdrawal. Conclusions: This case series indicates that bosentan can improve CF in SSc and that improvement is maintained in the long-term. Given the lack of effective therapies for SSc cutaneous involvement, larger studies should be addressed at confirming this benefit and an earlier use of this drug should be considered in these patients. Since bosentan has various beneficial effects in SSc it should be considered as a central therapeutic strategy in these patients.