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Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film and accompanied by symptoms such as ocular discomfort and visual disturbance. DED is one of the most common reasons for seeking medical care in the United States and across the world. Despite this, there are a limited number of pharmacologic therapies for the treatment of DED in the United States and Europe. This review examines the different pivotal trials for DED medications and the impact the vehicle in each trial.In recent clinical trials, the vehicle of the active formulation of the medication is often used as the active comparator. A literature review of published dry eye clinical trials was performed to identify the pivotal clinical trials of DED medications and to compare treatment effect and further understand the impact of the vehicle on clinical trial outcomes.The pivotal clinical trials for the currently approved treatments for dry eye have widely varying study designs. The variations include differences in inclusion criteria, outcome measures and efficacy endpoints, and whether or not the use of concomitant artificial tears is allowed. These differences make it difficult for accurate comparisons to be made between DED medications. Each trial demonstrated that the vehicle alone has some beneficial effect on signs and symptoms of dry eye disease.This review discusses the varying trial designs and vehicles used in the pivotal studies for the four approved dry eye medications in the United States and Europe, as well as novel vehicles under development and clinical trial recommendations.

Purpose: Characterize the safety and tolerability of lifitegrast ophthalmic solution 5.0% for the treatment of dry eye disease., Methods: Pooled data from five randomized controlled trials were analyzed. Key inclusion criteria were adults with dry eye disease (Schirmer tear test score ⩾1 and ⩽10 mm, eye dryness score ⩾40 (visual analog scale 0-100), corneal staining score ⩾2.0 (0-4 scale)). Participants were randomized to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 or 360 days. Treatment-emergent adverse events and drop comfort scores were assessed., Results: Overall, 2464 participants (lifitegrast, n = 1287; placebo, n = 1177) were included. Ocular treatment-emergent adverse events occurring in >5% in either group were instillation site irritation (lifitegrast, 15.2%; placebo, 2.8%), instillation site reaction (lifitegrast, 12.3%; placebo, 2.3%), and instillation site pain (lifitegrast, 9.8%; placebo, 2.1%); the most common (> 5%) nonocular treatment-emergent adverse event was dysgeusia (lifitegrast, 14.5%; placebo, 0.3%). The majority of treatment-emergent adverse events were mild to moderate in severity. Discontinuation due to treatment-emergent adverse events occurred in 7.0% (lifitegrast) versus 2.6% (placebo) of participants (ocular: 5.5% vs 1.5%; nonocular: 1.9% vs 1.1%). Drop comfort scores with lifitegrast improved within 3 min of instillation and the score at 3 min improved across visits (12-week trials (both eyes, day 84 vs 0): 2.0 vs 3.3; SONATA (day 360 vs 0): right eye, 1.2 vs 1.7; left eye, 1.2 vs 1.8)., Conclusion: Lifitegrast ophthalmic solution 5.0% appeared to be safe and well tolerated for the treatment of dry eye disease. Drop comfort with lifitegrast improved within 3 min of instillation.

Purpose: Lifitegrast is a lymphocyte function-associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED., Design: Twelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study., Participants: Adults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0-4 scale), eye dryness score (EDS) ≥40 (0-100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry., Methods: After a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days., Main Outcome Measures: The primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo., Results: In the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04-11.28; P = 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95% CI, 5.44-13.20; P < 0.0001) and 14 (TE, 7.85; 95% CI, 4.33-11.37; P < 0.0001). No statistically significant differences were observed in ODS between treatment groups at days 84, 42, or 14. A greater improvement was observed in lifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P = 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported., Conclusions: Lifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo., Methods: SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ≤10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma., Results: The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression., Conclusions: Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events.