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 your joints – see 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 faster.

We identified several potential biomarkers, including immune cells and proteins involved in inflammatory responses and immune system activation.

We are particularly interested in a specific cell type, namely T helper cells (Th). Th1 and Th17 cells are involved in the development of PsA and RA and we demonstrated that high proportions of Th1 cells were associated to a better response to TNFi in patients with PsA – Figure 2. These immune cells produce and secrete many inflammatory proteins called pro-inflammatory cytokines. Some of them are overexpressed in patients that respond poorly to TNFi. Some cytokines such as IL-17, IL-12 and IFNγ may be potential biomarkers of response to TNFi and are also involved in psoriasis pathogenesis. Thus, presence of psoriasis might also be a clinical marker of response to TNFi.

The next step is to investigate plasma to find a potential biomarker among hundreds of proteins, and to validate it with ELISA assays. 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.