Beyond TNF Inhibitors: New Pathways and Emerging Treatments for Psoriatic Arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by psoriasis, synovitis, enthesitis, spondylitis and association with other extra-articular manifestations. Chronic inflammation of involved tissues possibly leads to structural damage and to a reduction in function and quality of life. The treatment of PsA dramatically changed with the introduction of anti-tumor necrosis factor (TNF)-α drugs, which have been shown to reduce the symptoms and signs of the disease, and slow radiographic progression. However, some patients do not respond to anti-TNFα or have a loss of response. Recently, the discovery of new pathogenic mechanisms have made possible the development of new drugs that target pro-inflammatory cytokines, such as interleukin (IL)-12, IL-23 and IL-17, or interfere with cellular pathways involved in skin, joint and entheseal inflammation. New molecules, namely ustekinumab, secukinumab, and apremilast have shown efficacy and safety over the various components of the disease in randomized clinical trials. These drugs have been recently approved for the treatment of PsA and included in new treatment recommendations. Other molecules are currently being tested in phase III clinical trials and are potential new treatment options for PsA. The aim of this review is to update the new pathways involved in the development of the disease and the emerging treatments for PsA beyond TNFα inhibition.