By: Vicky Liu, PharmD Candidate c/o 2018
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On July 11, 2016, lifitegrast (Xiidra®), the first lymphocyte function-associated antigen 1 (LFA-1), was approved by FDA for the treatment of the signs and symptoms of dry eye disease. The risk for patients to develop dry eye syndrome increases with age, occurring in 5% of adults ages of 30 and 40 and 10-15% of adults over the age of 65. Untreated dry eye disease can cause pain, ulcers, or scars in the cornea, leading to difficulty in performing daily activities and decreased tolerance to dry areas.1
Keratoconjunctivitis sicca, commonly known as dry eye disease (DED), is a group of symptoms that consists of visual disturbances, eye discomfort, and dryness that is caused by tear film instability. The mechanism of DED is through an increase in osmolarity of the eye’s tear film and inflammation of its ocular surfaces and lacrimal glands. Studies have suggested that the inflammation is caused by CD4+ helper T-cells releasing pro-inflammatory cytokines and chemokines, directly damaging ocular tissues.2 Thus, lifitegrast was developed to inhibit T-cell activation from causing the inflammation cascade.
Lifitegrast binds to the LFA-1, a cell surface protein on leukocytes, and inhibits the interaction of LFA-1 with its cognate ligand: intercellular adhesion molecule-1 (ICAM-1). This is crucial because many patients with DED present with an overexpression of ICAM-1. Because lifitegrast blocks the interaction between LFA-1 and ICAM-1, the immunological synapse will not form and T-cells will not be activated to target tissues, such as the eye.3
OPUS-3 was a phase III randomized, double-blinded, placebo-controlled trial that reported the use of lifitegrast for DED. Patients 18 years and older with Schirmer tear test (without anesthesia) scores ≥1 and ≤10 mm, corneal fluorescein staining scores ≥2.0 (0-4 scale), eye dryness scores (EDS) ≥40 (0-100 visual analogue scale), and histories of artificial tear use within 30 days of study entry were part of the inclusion criteria for OPUS-3. The primary outcome was the difference in EDS from baseline to day 84, and study results demonstrated that patients taking lifitegrast demonstrated statistically significant results compared to the placebo group. The results from the 84th day were as follows: treatment effect, 7.16 (95% confidence interval, 3.04-11.28; P = 0.0007). In addition to improvement of eye dryness, other symptoms such as itchiness (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P=0.0048) were alleviated more with the intention-to-treat group than those in the placebo group. For adverse events, more than 5% of patients had instillation site irritation and reactions, categorized as mild to moderate severity. Notably, the most common non-ocular adverse event was dysgeusia (unusual taste sensation), which occurred in 12.9% of the participants.4
The American Academy of Ophthalmology has not updated its guidelines on DED since 2013 to include lifitegrast. However, lifitegrast may be a suitable alternative to treat patients with dry eye disease.
SOURCES:
- FDA approves new medication for dry eye disease. U.S. Food and Drug Administration. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm510720.htm. Updated 07/12/2016. Accessed on 03/14/2017.
- Abidi A, Shukla P, Ahmad A. Lifitegrast: a novel drug for treatment of dry eye disease. J Pharmacol Pharmacother. 2016;7(4):194-198. doi: 10.4103/0976-500X.195920.
- Xiidra® (lifitegrast) [package insert]. Lexington, MA; Shire USA Inc; Revised 07/01/2016.
- Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease: results of a phase III, randomized, double-masked, placebo-controlled trial (OPUS-3). Ophthalmology. 2017;124(1):53-60. doi: 10.1016/j.ophtha.2016.09.025.
