Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: combined evidence from 5 randomized controlled trials.

Abstract

Purpose : To evaluate the combined evidence from 5 clinical trials of the efficacy and safety of lifitegrast ophthalmic solution 5.0% versus placebo in subjects with dry eye disease (DED). Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist approved in the US for the treatment of signs and symptoms of DED.

Methods : Adults with DED were randomized to lifitegrast or placebo in 5 randomized, double-masked, placebo-controlled trials: 4 12-week efficacy/safety studies (phase 2, lifitegrast n=58, placebo n=58; phase 3 trials: OPUS-1, lifitegrast n=293, placebo n=295; OPUS-2, lifitegrast n=358, placebo n=360; OPUS-3, lifitegrast n=355, placebo n=356), and a 1-year safety study (SONATA, lifitegrast n=220, placebo n=111). Change from baseline to day 84 in DED signs and symptoms was evaluated across the 4 12-week studies. Key measures were the sign endpoint of inferior corneal staining score (ICSS; 0–4 point scale), and symptom endpoints of eye dryness score (EDS; visual analogue scale [VAS], 0–100 point scale), and visual-related function subscale of a symptom scale (0–4 point scale). Pooled safety data (lifitegrast n=1287, placebo n=1177) from all 5 trials were also analyzed.

Results : Lifitegrast improved ICSS vs placebo in the phase 2 study (secondary endpoint; treatment effect 0.35, nominal P=0.0209), OPUS-1 (co-primary; 0.24, P=0.0007), and OPUS-3 (ad hoc; 0.17, nominal P=0.0144). Lifitegrast reduced EDS (VAS) versus placebo in OPUS-2 (co-primary; 12.61, P<0.0001) and OPUS-3 (primary; 7.16, P=0.0007). The OPUS-1 co-primary symptom endpoint of visual-related function subscale, and the OPUS-2 co-primary sign endpoint of ICSS, did not achieve statistical significance. In the pooled safety analysis, total exposure was 415.65 person-years for lifitegrast, and 332.15 person-years for placebo. Adverse events were mostly mild or moderate in severity. There were no serious ocular treatment-emergent adverse events (TEAEs) and withdrawals due to TEAEs were infrequent (lifitegrast, 7.0%; placebo, 2.6%).

Conclusions : Lifitegrast improved signs and symptoms of DED in adults with DED and appeared to be well tolerated with no serious ocular TEAEs reported. The combined clinical evidence from these trials support the US FDA approval of lifitegrast as a first-in-class medication for the treatment of signs and symptoms of DED.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.