Improving the management of systemic sclerosis

Researchers at the UCL Centre for Rheumatology & Connective Tissue Disease have pioneered translational research in systemic sclerosis, resulting in better stratification, management and treatments for the condition.

Systemic sclerosis (SSc) is a rare but significant autoimmune disease, in which there is abnormal growth of connective tissue. This causes vascular damage and fibrosis. Fibrosis occurs in skin, the gastrointestinal tract and other internal organs, resulting in high mortality and major non-lethal morbidity.

We have defined the importance of regular proactive screening of cases for pulmonary complications (lung fibrosis and pulmonary hypertension). This has become standard in the management of SSc and has been adopted in all European scleroderma centres and incorporated in recommendations by international societies. As a result, historically poor outcomes have been positively impacted.

The biomarkers the researchers have described have enabled better prediction of complications such as scleroderma renal crisis and lung fibrosis, and identified subsets that benefit from more aggressive treatment. As a result of its definition of hallmark SSc antibodies associated with lung fibrosis and scleroderma renal disease, these tests are now routinely used in risk assessment of SSc worldwide. This permits more effective patient education and earlier engagement with other specialised hospital services.

The group has defined the cases of lung fibrosis in scleroderma that are most likely to benefit from immunosuppression and developed a simple staging system for lung fibrosis that is now used in most centres in UK and abroad and has been validated in two independent studies in the USA and Australia. This helps to avoid use of toxic immunosuppression in cases of SSc where this is unnecessary and enables the targetting of immunosuppressive therapy to more severe cases who gain the most benefit.

Furthermore, the group's ongoing programme of basic science, translational and clinical research has underpinned substantial advances in understanding vascular complications of SSc and has directly informed the development of new effective therapies. The best example of this is the use of endothelin receptor agonists (ERAs) in pulmonary arterial hypertension and digital ulcers. ERAs are now standard management for pulmonary arterial hypertension related to SSc. Worldwide, many thousands of patients have now benefitted from treatment with bosentan - around 11,000 in 2012 alone, according to sales figures.

This treatment reduces death rate by 30%. Thus the average survival for pulmonary arterial hypertension in SSc has improved from less than two years to more than five years from diagnosis. This can be estimated to have saved around 30 lives a year in our cohort of SSc cases and perhaps 150 lives per year in the UK. Furthermore, there is an important benefit in terms of quality of life and symptom burden as most patients with PAH treatment improve such that they can participate in normal activities again.

Digital ulcers are a significant complication of SSc. They are painful, and may take between three and 15 months to heal. Secondary infections may occur in 50% of cases, and recurring ulcers can be a major source of disability, interfering with the patient's daily activities and capacity to work. Digital ulcers can also lead to the chronic use of analgesics and antibiotics, and sometimes to hospitalisation and surgery (including digital amputation). Our work made a major contribution to the licensing of bosentan for digital ulcer disease. In 2012, over 5,000 digital ulcer patients were currently on this therapy.