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.
2014 ACR/SAA/SPARTAN recommendations for the management of axial spondyloarthritis, including ankylosing spondylitis, and children with the enthesitis-related arthritis form of juvenile idiopathic arthritis. Project plan. http://www.rheumatology.org/Portals/0/Files/Axial%20SpA%20Project%20Plan.pdf. Accessed 30 Aug 2016.
Reveille JD, Witter JP, Weisman MH. Prevalence of axial spondylarthritis in the United States: estimates from a cross-sectional survey. Arthritis Care Res (Hoboken). 2012;64:905–10. CrossRef
Wellcome Trust Case Control Consortium, Australo-Anglo-American Spondylitis Consortium (TASC), Burton PR, Clayton DG, Cardon LR, Craddock N, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet. 2007;39:1329–37. CrossRef
Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, et al. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum. 2004;50:650–9. CrossRefPubMed
Singh R, Aggarwal A, Misra R. Th1/Th17 cytokine profiles in patients with reactive arthritis/undifferentiated spondyloarthropathy. J Rheumatol. 2007;34:2285–90. PubMed
Londono J, Romero-Sanchez MC, Torres VG, Bautista WA, Fernandez DJ, de Avila QA, et al. The association between serum levels of potential biomarkers with the presence of factors related to the clinical activity and poor prognosis in spondyloarthritis. Rev Bras Reumatol. 2012;52:529–44.
Jansen DT, Hameetman M, van Bergen J, Huizinga TW, van der Heijde D, Toes RE, et al. IL-17-producing CD4 + T cells are increased in early, active axial spondyloarthritis including patients without imaging abnormalities. Rheumatology (Oxford). 2015;54:728–35. CrossRef
Lories RJ, Baeten DL. Differences in pathophysiology between rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol. 2009;27:S10–4. PubMed
Rohekar S, Chan J, Tse SM, Haroon N, Chandran V, Bessette L, et al. 2014 Update of the Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada treatment recommendations for the management of spondyloarthritis. Part II: specific management recommendations. J Rheumatol. 2015;42:665–81. CrossRefPubMed
Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler CL, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2016;76:79–87. CrossRefPubMedPubMedCentral
Genovese MC, Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, et al. A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2014;66:1693–704. CrossRefPubMed
Burmester GR, Durez P, Shestakova G, Genovese MC, Schulze-Koops H, Li Y, et al. Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monoclonal antibody secukinumab in active rheumatoid arthritis. Rheumatology (Oxford). 2016;55:49–55. CrossRef
Yao W, Sun Y, Wang X, Niu K. Elevated serum level of interleukin 17 in a population with prehypertension. J Clin Hypertens (Greenwich). 2015;17:770–4. CrossRef
Vargas-Alarcón G, Angeles-Martínez J, Villarreal-Molina T, Alvarez-León E, Posadas-Sánchez R, Cardoso-Saldaña G, et al. Interleukin-17A gene haplotypes are associated with risk of premature coronary artery disease in Mexican patients from the Genetics of Atherosclerotic Disease (GEA) study. PLoS One. 2015;10:e0114943. CrossRefPubMedPubMedCentral
Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693–700. CrossRefPubMedPubMedCentral
Reich K, Leonardi C, Langley RG, Warren RB, Bachelez H, Romiti R, et al. Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: a presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials. J Am Acad Dermatol. 2016. doi: 10.1016/j.jaad.2016.10.027.
- Mechanistic rationales for targeting interleukin-17A in spondyloarthritis
Siba P. Raychaudhuri
Smriti K. Raychaudhuri
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II