Biologic therapy of psoriatic arthritis

Abstract

Biologic medications, therapeutic proteins which inhibit or modulate proinfl ammatory immune cells and cytokines, have signifi cantly altered our ability to effectively treat psoriatic arthritis (PsA). The fi rst widely used biologics have been those targeting TNFα. Five agents, etanercept, infl iximab, adalimumab, golimumab and certolizumab have shown signifi cant benefi t in all clinical domains of PsA including arthritis, enthesitis, dactylitis, spondylitis, skin and nail disease, as well as inhibiting progressive joint destruction, improving function and quality of life. Although the anti-TNFs have been signifi cantly benefi cial for the majority of patients, some may not respond and other may lose effi cacy over time. Thus, it has been important to develop new medicines which target other key cytokines and immunologic pathways. Ustekinumab inhibits both IL12 and IL23 and thus is felt to work in both the TH1 and TH7 pathways of infl ammation. This agent has been approved for the treatment of PsA. An emerging group of therapies, the IL17 inhibitors, have demonstrated signifi cant effectiveness in psoriasis and also in musculoskeletal manifestations of PsA. Other medicines in development include the co-stimulatory blockade agent, abatacept and an emerging group of therapies which inhibit IL23. As modulators of immune cell function, these agents have the potential to increase risk for infection, as well as other side effects. These must be discussed with the patient and considered when determining overall risk benefi t regarding their use. Treatment strategies such as treating PsA early in disease course to reduce damage risk, treating-to-target and tight control, use of background methotrexate to reduce immunogenicity, and various cost-saving strategies are all being tested with biologic medicines for PsA.