New dry eye treatment demonstrates rapid onset symptomatic relief

Reviewed by Edward J. Holland, MD

Cincinnati, OH-In OPUS-3, the third Phase 3 randomized, placebo-controlled, double-masked study investigating lifitegrast ophthalmic solution 5.0% (Xiidra, Shire) for treatment of dry eye disease (DED), the novel immunomodulatory agent met its primary endpoint, significantly improving patient-reported eye dryness at day 84. Importantly, the benefit of lifitegrast compared with placebo for reducing the DED-related symptom was seen as early as day 14, said Edward J. Holland, MD.

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“The outcomes in OPUS-3 replicated the symptom improvement results observed in the Phase 3 OPUS-2 study and supported the FDA approval of lifitegrast,” said Dr. Holland, director of cornea services, Cincinnati Eye Institute, Cincinnati, OH, and an investigator in OPUS-3.

“It has been 13 years since a new medication was approved by the FDA for treatment of DED, and lifitegrast represents an important new option. Not only is it a unique immunomodulatory molecule that targets DED-related inflammation, but it provides the rapid symptomatic relief sought by patients who are bothered by DED.”

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Lifitegrast is a small molecule integrin antagonist that interferes with T-cell activation, migration, and release of inflammatory mediators by preventing binding between lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1). LFA-1 is a surface protein found on T-cells and ICAM-1 is a surface protein found on antigen presenting cells and upregulated on the surface of conjunctival endothelial and epithelial cells in eyes with DED.

OPUS-3 randomized 701 patients 1:1 to twice daily treatment with lifitegrast or placebo. Patients were eligible for inclusion if they had moderate-to-severe symptoms of DED as evidenced by an eye dryness score (EDS) ≥ 40 (rated on a visual analogue scale of 0 to 100 where 0 = none).

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Other key inclusion criteria required a Schirmer test without anesthesia result of ≥ 1 to ≤ 10 mm, corneal staining score ≥ 2.0, and a history of artificial tear use within 30 days of study entry.

Change in the EDS from baseline to day 84 was the primary endpoint, and the data analysis showed a statistically significant treatment effect (7.16 points; p = 0.0007) favoring lifitegrast. Mean change from baseline was -37.9 in the lifitegrast group and -30.7 for placebo-treated patients.

Secondary endpoint

Secondary endpoint analyses of the treatment effect at earlier follow-up visits showed rapid onset of symptom relief with lifitegrast and statistically significant benefit compared with placebo. Mean change in EDS from baseline to day 14 was -22.9 for lifitegrast and -15.0 for placebo (treatment effect 7.85; p < 0.0001) and from baseline to day 42 was -33.2 for lifitegrast and -23.9 for placebo (treatment effect = 9.32; p < 0.0001), reported Dr. Holland, who is also professor of ophthalmology, University of Cincinnati.

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The safety analyses corroborated findings from earlier studies showing lifitegrast was generally well-tolerated. There were no serious ocular treatment-emergent adverse events and the severity was mild for most ocular and non-ocular treatment-emergent adverse events.

The most common treatment-emergent adverse events with lifitegrast were instillation site irritation (burning) (18.2%), instillation site reaction (12.6%), and change in taste (12.9%). Incidence rates for these three adverse events in the placebo group were 3.1%, 5.4%, and 0.3%, respectively.

“The study also included patient ratings of drop comfort using an 11-point scale where 0 represents very comfortable and 10 is very uncomfortable. Within 3 minutes after instillation, drop comfort with instillation was rated < 3 by the majority of patients, and data collected at the serial follow-up visits showed the mean drop comfort scores improved over time,” said Dr. Holland.

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Edward J. Holland, MD

E: [email protected]

This article was adapted from Dr. Holland’s presentation at the 2016 annual meeting of the American Society of Cataract and Refractive Surgery Symposium. An article reporting the results of OPUS-3 has been accepted for publication in Ophthalmology. Dr. Holland is a consultant for Shire and for other companies that market products for DED.