Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study

Ophthalmology. 2014 Feb;121(2):475-83. doi: 10.1016/j.ophtha.2013.09.015. Epub 2013 Nov 26.

Abstract

Purpose: To assess the efficacy and safety of lifitegrast ophthalmic solution 5.0% compared with placebo in subjects with dry eye disease.

Design: Prospective, randomized, double-masked, placebo-controlled, parallel arm, multicenter clinical trial.

Participants: A total of 588 adult subjects with dry eye disease.

Methods: Eligible subjects were randomized 1:1 to receive topically administered lifitegrast (5.0%) or placebo (vehicle) twice daily for 84 days after a 14-day open-label placebo run-in period. After enrollment (day 0), subjects were evaluated at days 14, 42, and 84. Key objective (fluorescein and lissamine staining scores [Ora scales]) and subjective (Ocular Surface Disease Index [OSDI], 7-item visual analog scale, and ocular discomfort score [Ora scale]) measures were assessed at all visits.

Main outcome measures: The primary objective efficacy measure (sign) was mean change from baseline inferior corneal staining score (ICSS) at day 84. The co-primary subjective efficacy measure (symptom) was the mean change from baseline in the visual-related function subscale score of the Ocular Surface Disease Index (VR-OSDI). Supportive measures included corneal fluorescein scores (superior, central, total region) and conjunctival lissamine scores (nasal, temporal, total region) and symptom scores at day 84.

Results: The study met the primary objective efficacy ICSS end point in demonstrating superiority of lifitegrast compared with placebo (P = 0.0007). Lifitegrast significantly reduced corneal fluorescein staining (superior, P = 0.0392; total cornea, P = 0.0148) and conjunctival lissamine staining (nasal, P = 0.0039; total conjunctiva, P = 0.0086) at day 84 versus placebo. Significant (P < 0.05) improvements in nasal and total lissamine scores were observed at day 14 and maintained through day 84. The study did not meet the co-primary subjective VR-OSDI measure (P = 0.7894). However, significant improvements were observed at day 84 in ocular discomfort (P = 0.0273) and eye dryness (P = 0.0291), the most common and severe symptoms reported at baseline in both groups. There were no unanticipated or serious ocular adverse events (AEs). The most frequent reported ocular AEs were transient intermittent instillation site symptoms (irritation, discomfort) primarily on the initial lifitegrast dose at day 0.

Conclusions: Lifitegrast ophthalmic solution 5.0% significantly reduced corneal fluorescein and conjunctival lissamine staining and improved symptoms of ocular discomfort and eye dryness compared with placebo when administered twice daily over 84 days.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adult
  • Aged
  • Aged, 80 and over
  • Conjunctiva / metabolism
  • Cornea / metabolism
  • Double-Blind Method
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / physiopathology
  • Female
  • Fluorescein / metabolism
  • Fluorometry
  • Humans
  • Lissamine Green Dyes / metabolism
  • Lymphocyte Function-Associated Antigen-1 / drug effects*
  • Male
  • Middle Aged
  • Ophthalmic Solutions
  • Phenylalanine / administration & dosage
  • Phenylalanine / adverse effects
  • Phenylalanine / analogs & derivatives*
  • Prospective Studies
  • Staining and Labeling
  • Sulfones / administration & dosage*
  • Sulfones / adverse effects
  • Treatment Outcome
  • Young Adult

Substances

  • Lissamine Green Dyes
  • Lymphocyte Function-Associated Antigen-1
  • Ophthalmic Solutions
  • Sulfones
  • lifitegrast
  • Phenylalanine
  • Fluorescein