Abstract
Purpose:
To report the results of a pivotal study comparing lifitegrast to placebo in subjects with dry eye disease (DED). DED is associated with ocular surface inflammation leading to symptoms of discomfort. Lifitegrast is an investigational drug targeting the integrin lymphocyte antigen-1 (LFA-1) and inhibits binding to its cognate ligand, intracellular adhesion molecule-1 (ICAM-1) by serving as an ICAM-1 decoy. LFA-1/ICAM-1 interactions are key steps regulating T-cell mediated inflammation.
Methods:
A randomized, double-masked, placebo-controlled study enrolled 588 dry eye subjects randomized 1:1 to lifitegrast or placebo (vehicle) administered BID for 84 days. Eligibility included no active lid margin disease, STT ≥ 1 and ≤ 10 mm, and worsening of fluorescein staining and symptoms upon exposure to a controlled adverse environment (CAE™). Corneal fluorescein / lissamine staining parameters (Ora) and symptoms (visual analog scale [dryness, burning/stinging, photophobia, FB sensation, pain, blurred vision, itching], ocular discomfort (Ora)) were collected at baseline, Day 14, 42, and 84.
Results:
Lifitegrast demonstrated superiority to placebo in reducing inferior (P=0.0007), superior (P=0.0392), and total corneal staining (P=0.0148), baseline to Day 84. This was accompanied by significant improvements in nasal (P=0.0039), temporal (P=0.0936) and total (P=0.0285) lissamine staining, baseline to Day 84. Onset of action was observed as early as Day 14 and maintained through Day 84. The chief medical complaints of dryness and discomfort were significantly improved at Day 84 (P=0.0291, P=0.0273, respectively). There were no serious ocular adverse events (AE). The most common ocular AE were instillation site complaints (e.g., irritation) upon the initial dose of lifitegrast at Day 0. No significant changes were observed in IOP, BCVA, slit-lamp, dilated fundoscopy, and corneal sensitivity. The most common non-ocular AE was dysgeusia (taste) in ∼13% of lifitegrast subjects.
Conclusions:
Lifitegrast 5.0% ophthalmic solution demonstrated superiority to placebo in reduction of corneal fluorescein and conjunctival lissamine staining - key clinical parameters of dry eye disease; reductions in staining were associated with significant improvements in key symptoms. Lifitegrast appears safe and well-tolerated when administered BID for 84 days.
Keywords: 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials •
486 cornea: tears/tear film/dry eye •
479 cornea: clinical science