Unravelling the complexity of psoriatic arthritis on a journey towards precision medicine

Abstract

Psoriatic Arthritis (PsA) is a complex, musculoskeletal disease characterized by a heterogeneous clinical phenotype and variable disease course. With new treatment options emerging, it has become difficult for rheumatologists to know which therapy is best for which patient. Postponing efficacious therapy - even for six months - can result in progression of joint erosions, decreased long-term physical function and reduced risk of medication-free remission. Hence, there is an urgent clinical need to tailor medical treatment to individual patients. This thesis discusses recent advances to unravel the complexity of PsA, on a journey towards precision medicine. The clinical work presented in this thesis provides indirect evidence for the efficacy of conventional synthetic disease modifying anti-rheumatic drugs in PsA. The results of a literature review and experimental laboratory research underline the importance of the adaptive immune system in disease pathogenesis. Two new dysregulated T cell mechanisms are discovered, which could be investigated as therapeutic targets. Furthermore, by clinical research and reviewing literature the need for robust predictors is confirmed, both for the development of PsA in psoriasis patients and for the response to therapy. In recent years, advancing experimental methods, analytical techniques and computational modeling approaches have enabled researchers to study an increasing range of clinical, (epi)genetic, immune, and other biomarkers. Future research is warranted to discover and validate robust prediction models to facilitate personalized treatment and prevention of PsA.