Mechanistic rationales for targeting interleukin-17A in spondyloarthritis

Abstract

The term spondyloarthritis (SpA) is used to describe a group of inflammatory autoimmune diseases, including ankylosing spondylitis and psoriatic arthritis, with common genetic risk factors and clinical features. SpA is clinically distinct from rheumatoid arthritis and typically affects the spine, sacroiliac joints, entheses, and, less commonly, peripheral joints. Although the pathogenesis of SpA is not fully understood, recent findings have identified the interleukin (IL)-17 pathway as a key mediator of disease pathogenesis. Clinical evidence for the efficacy of IL-17A inhibition by biologic agents was initially shown in patients with chronic plaque psoriasis, another autoimmune disease mediated by the IL-17 pathway. Subsequently, similar positive efficacy for inhibition of IL-17A was seen in patients with ankylosing spondylitis and psoriatic arthritis. Inhibition of IL-17A may also improve cardiovascular and metabolic comorbidities often found in patients with SpA because studies have linked these disorders to the IL-17 pathway. In this review, we will examine key preclinical studies that demonstrated the mechanistic role of IL-17A in the development SpA and discuss how these observations were translated into clinical practice.

Keywords: Ankylosing spondylitis; Clinical practice; IL-17A inhibition; Interleukin-17; Preclinical studies; Psoriatic arthritis; Review; Spondyloarthritis.

Fig. 1

Pathogenic role of IL-17A in SpA [12]. Reprinted from Raychaudhuri SP. Role of IL-17 in psoriasis and psoriatic arthritis. Clin Rev Allergy Immunol. 2013;44:183–93, with permission of Springer. APC antigen-presenting cell, ICAM-1 intercellular adhesion molecule-1, IL interleukin, IFN interferon, MMP3 matrix metalloproteinase 3, TGF transforming growth factor, RANKL receptor activator of nuclear factor-κB ligand, Th T-helper, TNF tumor necrosis factor