The Bench-to-Bedside Story of IL-17 and the Therapeutic Efficacy of its Targeting in Spondyloarthritis.
TNF-blocking biologics have revolutionized the care of patients with spondyloarthritis, a group of clinically overlapping conditions that includes ankylosing spondylitis and psoriatic arthritis. However, incomplete response rates speak to the need for alternative therapeutic approaches. Over the last decade, animal models, genetics, and translational studies have implicated the excessive production of a pro-inflammatory cytokine interleukin-17 (IL-17) along with another IL-17-promoting cytokine IL-23 in the pathogenesis of spondyloarthritis. Genome-wide studies identified disease associations with multiple genes regulating IL-23/IL-17 immune pathway activity. Direct examination of the patient blood and tissues revealed excessive IL-17 and IL-23 production by diverse cell types. Murine models both underscored the sufficiency of excess IL-23 in driving disease phenotype and predicted utility in IL-23/IL-17 pathway blockade. However, the clinical efficacy of agents such as secukinumab and ustekinumab, which block IL-17 and IL-23/IL-12 respectively, provided exciting proof of concept.
Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, 600 Highland Ave, Madison, WI, 53792-4108, USA. Jsmith27@pediatrics.wisc.edu.
Judith A
JA
Smith
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D058990:Molecular Targeted Therapy / Q000379:methods*; D025241:Spondylarthritis / Q000188:drug therapy* / Q000276:immunology; D000069549:Ustekinumab / Q000494:pharmacology / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D020381:Interleukin-17; C555450:secukinumab; D000069549:Ustekinumab
Ankylosing spondylitis; IL-17; IL-23; Psoriatic arthritis; Secukinumab; Spondyloarthritis; Ustekinumab