Biomarkers for the PARIS study: Psoriatic Arthritis - Resistance to TNF Inhibitor Study

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease and patients suffer from joint and spinal pain because of immune cell infiltration and expansion in skin and synovium. These cells release a large panel of pro inflammatory factors responsible for the inflammation, as cytokines and chemokines. We can cite for instance Tumor Necrosis Factor $\alpha$ (TNF$\alpha$), Interleukin (IL)-17, IL-23 and IL-1$\beta$ released by Peripheral Blood Mononuclear Cells (PBMC) such as CD4+ and CD8+ T cells, neutrophils and macrophages.

PsA occurs in 30% of people with psoriasis. It diminishes considerably the quality of life of patients and serious desabiliting effects are present on the peripheral joints, spine, tendon insertion and fingers. PsA accounts for 20% of referrals to the early arthritis clinic and early recognition and intervention is crucial to patient outcome. Currently, diagnosis of PsA is not optimal because there are no precise tests available to detect or recognize the disease.

No curative treatments are available for PsA. Non Steroidal Anti-Inflammatory drugs (NSAID) are used as first approach for topical therapy for psoriasis and to reduce pain; the next step is administration of Disease-Modifying Anti-Rheumatic Drugs (DMARDs) alone, and then in combination; and finally, biologic drugs targeting specific cytokines and signaling pathways, such as TNF$\alpha$ inhibitors or IL-17 inhibitors, are administrated if patients fail to respond NSAID and DMARDs. However, at least 40% of patients with PsA have only a partial response or fail to respond to biologics. The aim of the PSAPS study is to investigate whether blood inflammatory markers can predict if patients with PsA will respond or not to TNF$\alpha$ inhibitors, and consequently to help choosing the optimal biologic therapy for patients, individually.

First literature research has highlighted several promising inflammatory factors:

• Human Serum Albumin and its receptor FcRn (Neonatal Fc Receptor)
• Alarmins, such as S100 family members and HMGB1
• Advanced Glycation End-products (AGEs)
• Lymphotoxin α, the second ligand to TNF Receptor.

Arrays allowing the detection of hundreds of pro inflammatory markers can also be used to analyze serum of patients at a large scale, and IL-17 pathway will be screen in detail to understand why some patients respond to IL-17 inhibitors while they do not respond to TNF$\alpha$-inhibitors.