Quantifying the burden of systemic sclerosis in Australia: From data linkage to patient reported outcomes

© 2018 Dr Kathleen MorrisroeSystemic sclerosis (SSc) is a chronic incurable autoimmune disease characterised by vasculopathy and fibrosis and is arguably the most devastating of the rheumatological diseases, with the potential to irreparably damage multiple organ systems and shorten life expectancy by an average of two decades. Pulmonary arterial hypertension (SSc-PAH) is the leading cause of SSc-related death and the major contributor to years of life lost. Worldwide prevalence of SSc varies with estimates ranging from 7/million to 489/million and incidence from 0.6/million/year to 122/million/year. There appears to be a north-south gradient in the geographical variation of SSc, with Australia having one of the highest reported prevalence worldwide (21.1 per 100,000). The true ‘burden’ of SSc in Australia remains unquantified, including its economic burden and impact on health-related quality of life (HRQoL). Studies of these nature are essential for clinicians and health policy makers in order to quantify the burden of a disease and to assess the outcomes of health policies and interventions. My thesis is composed of a series of clinical studies aimed at quantifying the burden of SSc in Australia by means of a nationwide data linkage project and evaluating patient reported outcomes. Firstly, I quantify the direct healthcare cost associated with SSc and its determinants by means of data linkage and show that SSc, despite its low prevalence, is associated with a substantial economic burden resulting from healthcare utilisation. Direct costs as a consequence of healthcare utilisation amount to an annual cost per patient of AUD$79,202.47, with SSc-PAH and gastrointestinal manifestations being the main drivers of cost. Secondly, I quantify the indirect cost resulting from work disability including both unemployment and lost work productivity in SSc patients. Amongst our SSc cohort, unemployment accounts for a societal cost of AUD$786,339.84 per person for average earnings, while for employed patients the cost per patient from lost productivity from a societal perspective is AUD$8,024.20. My thesis also assesses the impact of SSc on patient reported HRQoL. I highlight the negative impact SSc has on HRQoL early in the disease process, particularly in those with SSc-PAH and diffuse cutaneous disease subtype. Lastly, I explore the epidemiology of SSc-PAH in our SSc cohort as I found that SSc-PAH is a significant determinant of both direct and indirect economic burden, in addition to poor HRQoL. My results demonstrate that PAH is a common manifestation of SSc that despite annual screening and advanced PAH therapy is associated with poor survival and diminished HRQoL. I create a predictive model for the development of SSc-PAH, which may aid in identifying SSc patients at increased risk of PAH who should be monitored more closely. Furthermore, I identify determinants of survival in SSc-PAH and show that combination PAH therapy together with anticoagulation, compared with monotherapy without anticoagulation is associated with the highest survival benefit in SSc-PAH. My thesis lays the foundation for further research, particularly in the area of SSc-PAH treatment, work inclusion and addressing specific aspects of HRQoL in SSc patients, with the ultimate aim of improving patient outcomes and reducing the impact of this devastating disease