• Bosentan is oral drug with vasodilatory actions licensed to prevent
new digital ulcers in patients with systemic sclerosis. Bosentan is
designated an orphan drug.

• Systemic sclerosis is a rare condition characterised by excessive
fibrosis of the vasculature and skin resulting in skin thickening,
vascular constriction, and eventually organ death. Digital ulcers are
a common manifestation resulting from vascular constriction and
necrosis in the fingers and toes, causing pain and often amputation.

• Typical management relies upon lifestyle changes and treatment
with vasodilator drugs such as calcium channel blockers. More
severe cases may require treatment with intravenous prostacyclin
analogues in an acute setting.

• Bosentan has been evaluated in two short-term placebo-controlled
randomised controlled trials of patients with systemic sclerosis and
digital ulcers. The evidence indicates modest and limited efficacy,
demonstrating little or no effect on existing ulcers but a reduction in
the emergence of new digital ulcers. Small but statistically significant
improvements in hand function have also been demonstrated.
Longer-term non-comparative data indicate that initial efficacy is
maintained.

• Bosentan has a fairly well established adverse effect profile. Liver
enzyme abnormalities are common, affecting about 10% of patients
and resulting in treatment cessation in about 5%. Other common
adverse effects include oedema, fluid retention, anaemia, and
gastrointestinal effects.

• Bosentan is an expensive drug with an annual cost in excess of
£19,000 per patient. In addition, patients will require monthly liver
enzyme function tests. Off-set costs may be substantive if patients
are withdrawn from prostacyclin therapy with an attendant reduction
in medical care. Conventional oral therapy for digital ulcers and the
commonly associated Raynaud’s phenomenon are generally of low
acquisition cost.

• The prevalence of severe digital ulcer disease with systemic
sclerosis is estimated at a mean of about two patients per primary
care trust within NHS North East.