Lifitegrast 5.0% for the treatment of dry eye disease: responder analysis for reductions in eye dryness score in two phase 3 randomized controlled trials

Session Details

Session Title: Cornea: Medical

Session Date/Time: Tuesday 10/10/2017 | 08:00-10:30

Paper Time: 09:36

Venue: Room 3.6

First Author: : E. Donnenfeld USA

Co Author(s): :    E. Holland   C. Baudouin   K. Nichols   P. Karpecki   M. Hamdani   M. Roy   A. Shojaei Shire  

Abstract Details

Purpose:

Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist, recently approved in the US for the treatment of signs and symptoms of dry eye disease (DED). Results from five randomized controlled trials demonstrated the efficacy and safety of lifitegrast in the treatment of DED. In order to provide further clinical context to the trial data, we evaluated the proportion of subjects who achieved defined response thresholds for reductions in eye dryness in two trials of similar design.

Setting:

Two phase-3, twelve-week, randomized, double-masked, placebo-controlled trials (OPUS-2, OPUS-3) were conducted among subjects with DED at multiple sites in the United States (2012–2015). In the OPUS-2 trial, n=358 subjects were randomized to lifitegrast and n=360 to placebo; in OPUS-3, n=355 subjects were randomized to lifitegrast and n=356 to placebo.

Methods:

Clinical meaningfulness of eye dryness score (EDS, VAS [visual analogue scale], 0–100) reduction was assessed in two approaches, as absolute change from baseline (≥10-points, ≥15-points, ≥20-points) and as percent change from baseline (≥30%, ≥50%, ≥70%). The proportions of subjects achieving these thresholds for reduction in EDS after 14, 42 or 84 days of lifitegrast/placebo treatment were evaluated. Enrolled subjects in both trials had EDS ≥40, corneal staining score ≥2.0 (0–4 scale), and a history of artificial tear use at entry. The analysis was based on the intent-to-treat population with last observation carried forward. All reported P-values are nominal.

Results:

In OPUS-2, the proportion of subjects with ≥15-points reduction in EDS, lifitegrast versus placebo, was: day-14, 56.1% versus 38.6%; day-42, 67.6%, 49.7%; day-84, 74.3%, 56.9% (all P<0.0001). Proportion of subjects with ≥30% reduction was: day-14, 47.5%, 30.6%; day-42, 59.8%, 41.1%; day-84, 68.7%, 48.9% (all P<0.0001). In OPUS-3, the proportion of subjects with ≥15-points reduction in EDS, lifitegrast versus placebo, was: day-14, 57.7% versus 42.5% (P<0.0001); day-42, 74.2%, 56.7% (P<0.0001); day-84, 79.9%, 68.3% (P=0.0004). Proportion with ≥30% response was: day-14, 52.6%, 35.1%; day-42, 67.1%, 49.0%; day-84, 74.2%, 60.1% (all P<0.0001). For other thresholds, lifitegrast response was also significantly better than placebo.

Conclusions:

In both the OPUS-2 and OPUS-3 trials, a significantly higher proportion of adults with DED achieved reductions in eye dryness score with lifitegrast ophthalmic solution 5.0% compared with placebo using different response thresholds based on the percentage change and the absolute change from baseline. Notably, lifitegrast showed a higher response rate as early as day 14 after treatment initiation.

Financial Disclosure:

has significant investment interest in a company producing, developing or supplying product or procedure presented, travel has been funded, fully or partially, by a competing company, research is funded, fully or partially, by a competing company, research is funded, fully or partially, by a company producing, developing or supplying the product or procedure presented, receives consulting fees, retainer, or contract payments from a competing company, receives consulting fees, retainer, or contract payments from a company producing, developing or supplying the product or procedure presented, is employed by a forNONEprofit company with an interest in the subject of the presentation, has significant investment interest in a competing company