title: Lifitegrast, a Novel Integrin Antagonist for Treatment of Dry Eye Disease.
abstract: The etiology of dry eye disease (DED) is complex and not yet fully understood, but the disease is now recognized as being associated with ocular surface inflammation. The latest advances in the understanding of the pathophysiology of DED have directed the focus of recent drug development to target the inflammatory pathways involved in the disease. Lifitegrast is a novel small molecule integrin antagonist that inhibits T cell-mediated inflammation by blocking the binding of two important cell surface proteins (lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1), thus lessening overall inflammatory responses. This review highlights the role of T cells and integrins in the inflammatory process involved in the pathophysiology of DED and outlines the scientific rationale for the role of lifitegrast. In addition, the preclinical development, pharmacological properties, clinical efficacy, and safety of lifitegrast are described.
authors.affiliation: Ocular Surface Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: vperez4@med.miami.edu.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Perez
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Shojaei
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Haque
mesh_terms: D002448:Cell Adhesion; D015352:Dry Eye Syndromes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1; D010649:Phenylalanine / Q000031:analogs & derivatives; D013450:Sulfones
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D013450:Sulfones; C575157:lifitegrast; D018799:Intercellular Adhesion Molecule-1; D010649:Phenylalanine
keywords: ICAM-1; LFA-1; dry eye disease; inflammation; integrin antagonist; lifitegrast