Managed Care January 2017 : Cover 2

XIIDRA HAS A MECHANISM OF ACTION THAT BLOCKS THE INTERACTION OF LFA-1 AND ICAM-1 1 Lifi tegrast, the active ingredient in Xiidra, is designed to specifi cally block the interaction of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), which is a key mediator of the infl ammation behind Dry Eye Disease (DED). 1-3 ICAM-1 can play an important role in DED infl ammation Lifi tegrast binds to LFA-1, a cell surface protein found on leukocytes, and blocks the interaction of LFA-1 with ICAM-1. 1 ICAM-1 may be overexpressed in corneal and conjunctival tissues in DED. LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse, resulting in T-cell activation and migration to target tissues. 1 In vitro studies have shown that Xiidra may inhibit the recruitment of previously activated T cells, the activation of newly recruited T cells, and the release of pro-infl ammatory cytokines—interrupting the perpetual cycle of infl ammation. 1,4 The exact mechanism of action of lifi tegrast in DED is not known. 1 ICAM-1 LFA-1 Xiidra is the fi rst in a new class of drugs called LFA-1 antagonists. 5 Indication Xiidra (lifi tegrast ophthalmic solution) 5% is indicated for the treatment of the signs and symptoms of dry eye disease. Xiidra Figure 1. LFA-1 binds with ICAM-1 on the ocular surface Important Safety Information In 5 clinical trials, the most common adverse reactions reported in 5-25% of patients were instillation site irritation, dysgeusia and reduced visual acuity. Other adverse reactions reported in 1% to 5% of the patients were blurred vision, conjunctival hyperemia, eye irritation, headache, increased lacrimation, eye discharge, eye discomfort, eye pruritus and sinusitis. To avoid the potential for eye injury or contamination of the solution, patients should not touch the tip of the single-use container to their eye or to any surface. Contact lenses should be removed prior to the administration of Xiidra and may be reinserted 15 minutes following administration. Safety and effi cacy in pediatric patients below the age of 17 years have not been established. Please see Brief Summary of Prescribing Information on next page. References: 1. Xiidra [package insert]. Lexington, MA: Shire US Inc.; 2016. 2. Gao J, Morgan G, Tieu D, et al. ICAM-1 expression predisposes ocular tissues to immune-based infl ammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice. Exp Eye Res. 2004;78(4):823-835. 3. Zhang Y, Wang H. Integrin signalling and function in immune cells. Immunology. 2012;135(4):268-275. 4. DEWS Research Subcommittee. Research in dry eye: report of the Research Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):179-193. 5. FDA approves new medication for dry eye disease [news release]. Washington, DC: US Food and Drug Administration; July 12, 2016. Accessed October 19, 2016. LFA-1 ICAM-1 Figure 2. Lifi tegrast blocks the interaction of LFA-1 and ICAM-1 Marks designated ® and ™ are owned by Shire or an affiliated company. ©2016 Shire US Inc., Lexington, MA 02421 S17551 11/16


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