Comorbidity and Patient-Centred Health Outcomes in Psoriatic Arthritis

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis, with a wide range of phenotypic expression. Comorbid medical conditions may play a role in disease expression and outcomes. Cardiovascular comorbidities are common, and obesity associated with increased risk of incident PsA, and poorer response to therapy. In this thesis we aim to test the following hypotheses: 1. Comorbid conditions including obesity are associated with chronic systemic inflammation and adversely impact outcomes in PsA. 2. Adipokines contribute to systemic inflammation, may serve as biomarkers for disease phenotype in PsA, and be associated with disease activity. Analysis from the Australian Rheumatology Association Database highlights the high prevalence of comorbidity in PsA. Physical inactivity was common, and uptake of healthy lifestyle modifications was low. Treatment with biologic disease-modifying therapy was associated with lower rates of cardiovascular events, suggesting reduction of chronic inflammation may improve patient outcomes. We explored the contribution of joint stiffness and adipokines to patient outcomes in PsA. Stiffness was an important aspect of patient experience, and independently predicted physical function. Systematic review of circulating adipokines in PsA revealed conflicting data. Existing studies are heterogeneous in design and quality, and none report phenotypic subgroups. Preliminary results from a PsA cohort study found obesity was associated with higher active joint counts, and adipokine levels varied with phenotypic subgroups. This thesis highlights the burden of comorbidity in PsA, and supports the hypotheses that chronic systemic inflammation both contributes to cardiovascular comorbidity, and is driven in obesity by adipokines. Further research is needed to define the impact of comorbidity on phenotype and response to treatment in PsA, which may contribute to development of personalised, patient-centred management strategies.