PARIS STUDY: PSORIATIC ARTHRITIS – RESISTANCE TO TNF INHIBITORS STUDY

Anaïs Makos, Jan Herman Kuiper, Roshan Amarasena, Oksana Kehoe

Funded by RJAH Hospital Charitable Fund

Psoriatic Arthritis (PsA) is a disease that can cause pain, stiffness and swelling of the joints and spine. It develops when the immune system attacks the healthy cells of the body, this is what we call inflammatory arthritis. Stiffness, swelling and pain can occur in all joints i.e. hands, wrist, shoulders, hips, knees, ankles, feet, and in your spine. In PsA, the cells in blood and joints produce an excess amount of a small protein called Tumor Necrosis Factor (TNF) which is responsible for the swelling and pain of the joints (Figure 1). TNF inhibitors (TNFi) are the first-line biologic treatments able to block this protein to reduce the inflammation. They are prescribed by rheumatologists when conventional treatment does not show any efficiency. However, about 40% of patients do not or only partially respond to TNFi.

The aim of the PARIS study is to find potential biomarkers in blood of patients with PsA to predict response to TNFi. The study also aims to analyse blood from patients with rheumatoid arthritis (RA) to validate, or not, the potential biomarkers in different type of arthritis. A validated biomarker for TNFi response could help clinicians choose a more appropriate treatment in first instance and would improve patients’ quality of life quicker.

We identified several potential biomarkers, including immune cells and proteins involved in inflammatory responses and immune system activation. Proteomics analysis highlighted key pathways involved in treatment response: complement system, MMPs, alarmins, and stress response proteins (Figure 2).

Finally, a large data analysis will be performed, using UK Biobank data, to determine how diet, physical activity and comorbidities could be involved in disease severity and lead to the use of biologic drugs such as TNFi.